Nuclear envelope proteins in cancer: revisiting the significance of LEM-domain proteins

Abstract

Nuclear envelope dysfunction is increasingly recognized as a driver of cancer-associated alterations in chromatin organization, genome stability, and mechanotransduction. Among inner nuclear membrane components are the LEM-domain (LEM-D) proteins LAP2/TMPO, emerin (EMD), LEMD1, LEMD2, MAN1/LEMD3, ANKLE1, and ANKLE2. Accumulating evidence links dysregulation of these proteins to hallmark cancer processes, including cell-cycle control, epithelial–mesenchymal transition, genome instability, and therapeutic resistance. This review synthesizes recent mechanistic and translational findings on LEM-D proteins in cancer, highlighting isoform-specific functions, context-dependent oncogenic versus tumor-suppressive roles, and convergence on key pathways such as Wnt/β-catenin, PI3K/AKT, MAPK, and TGF-β signaling. Concrete evidence for prognostic value varies across the LEM-D proteins. While much of the current evidence derives from transcript-level and preclinical studies, emerging data suggest that LEM-D proteins contribute to nuclear stress adaptation and may represent context-dependent therapeutic vulnerabilities. We discuss their prognostic and predictive potential, critically evaluate limitations in current datasets, and present a unifying framework linking LEM-D dysfunction to genome instability, altered signalling, and therapy resistance. Thus, despite growing evidence of therapeutic potential, these proteins are better positioned as biomarkers to guide current therapies.

1 Introduction

The eukaryotic nuclear envelope (NE) consists of three interconnected major components with varying morphology—the nuclear lamina, the inner and outer nuclear membranes, and the nuclear pore complexes. The inner nuclear membrane is closely associated with the nuclear lamina, while the outer nuclear membrane is continuous with the rough and smooth endoplasmic reticulum (Lin et al., 2000). The LEM domain (LEM-D) proteins termed from the initial members—LAP2, Emerin (EMD), MAN1 — are a family of inner nuclear membrane proteins sharing a common ∼45-residue LEM-domain, a structural motif mediating association with the DNA associated protein Barrier-to-Autointegration Factor (BAF). In mammals, these proteins are encoded by 7 genes, namely, LEMD1, LEMD2, LAP2, EMD, MAN1, ANKLE1, and ANKLE2. Despite sharing only 18% similarity, both domains contain similar 3D structures, consisting of two large parallel helices and a three-residue N-terminal helix joined by conserved hydrophobic amino acids. Figure 1 shows the three-dimensional (3D) structure of the LEM-domain (PDB ID 1H9F) and the LEM-like domain of LAP2 (PDB ID 1H9E) (Laguri et al., 2001). The shared hydrophobic core maintains the same three-helix fold in both structures. In LEM, the domain-specific residues contribute to a relatively more charged solvent-exposed surface while and the LEM-like domain-specific residues define the distinct hydrophobic core organization of the LEM-like domain.

FIGURE 1

The LEM-D proteins are essential parts of the inner membrane and have one or two transmembrane domains; however, ANKLE1 lacks a transmembrane domain and shuttles between the nucleoplasm and cytoplasm, while LAP2α and γ isoforms localize to the nucleoplasm (Brachner and Foisner, 2011). Most of the LEM-D proteins connect the membrane to the lamina scaffold by binding lamins within the lamina. These proteins recruit and modulate signaling molecules (Wilson and Berk, 2010), including SMADS that are implicated in the signaling pathways of bone morphogenetic protein (BMP) and transforming growth factor beta (TGFß) (Lin et al., 2005; Pan et al., 2005), Histone deacetylase 3 (HDAC3) (Demmerle et al., 2012), the Lmo7 transcription factor (Dedeic et al., 2011), the Germ Cell Less (GCL) transcriptional repressor (Holaska et al., 2003; Nili et al., 2001), and ß-catenin, a transcriptional co-activator of the Wnt signaling pathway (Markiewicz et al., 2006). Figure 2 illustrates the main biological functions of the LEM-D proteins.

FIGURE 2

Besides the conserved LEM-D which is typically located at the N-terminal end across the seven LEM-D proteins, most of the LEM-D subtypes have additional domains mostly in the C-terminal end (Figure 3). For instance, LAP2 harbors a LEM-like domain that facilitates direct DNA binding (Cai et al., 2001) while LEM2 and MAN1 carry carboxyl-terminal winged-helix ‘MSC’ (MAN1/Src1p/C-terminal) motif (Caputo et al., 2006). MAN1 has a predicted RRM-like protein interaction domain termed UHM (U2AF homology motif) (Caputo et al., 2006; Kondé et al., 2010). ANKLE1 and ANKLE2 carry ankyrin repeats which mediate protein-protein interactions (Li et al., 2006) with various structural and regulatory proteins (Demmerle et al., 2012). Other domains include the GIY-YIG nuclease domains in ANKLE1, the SMAD-binding motif in MAN1, lamin interaction motifs in LEMD2, and the β-catenin regulatory interfaces in EMD (Figure 3). These additional motifs underlie the functional diversity of LEM-D proteins in cancer, enabling integration of nuclear structure with transcriptional regulation, cytoskeletal coupling, and stress-response signaling.

FIGURE 3

2 Nuclear envelope mechanics, instability, and cancer progression

In cancer, NE defects are associated with chromatin dysfunction and malignant phenotype (Isermann and Lammerding, 2017; Var et al., 2012). Thus, nuclear deformation and chromatin alterations have been used for cancer diagnosis and staging for decades (Zink et al., 2004). Specifically, nuclear morphology, size, texture, and protein composition are frequently altered in malignant cells. Unlike the typically round nucleus with a smooth shape seen in normal cells, the nucleus in cancer cells may feature grooves, folds, or indentations; the chromatin may clump together or disperse; and the nucleolus may increase in size (Zink et al., 2004; Denais and Lammerding, 2014). Cells lacking particular NE proteins or expressing mutant NE proteins have similar nuclear morphological deformations, pointing to a potential link between dysregulated NE proteins and cancer pathogenesis (Zink et al., 2004; Muchir et al., 2004; Vigouroux et al., 2001). Additionally, mutations in nuclear lamina proteins disrupt nucleo-cytoskeletal connections, compromising the mechanical signaling required for migration (Friedl et al., 2011). During migration through dense extracellular matrices, cancer cells are frequently subjected to transient NE rupture (Denais et al., 2016). Such rupture events permit cytoplasmic–nuclear mixing, trigger DNA damage accumulation, and exacerbate replication stress, ultimately contributing to genomic instability. Additionally, chromosomal instability arising from nuclear defects has been shown to promote metastatic progression through cytosolic DNA sensing pathways (Bakhoum et al., 2018). Recent studies further demonstrate that micronuclei formed following NE rupture are highly prone to chromosomal rearrangements, including chromothripsis, thereby accelerating tumor evolution (Umbreit et al., 2020).

NE rupture is followed by repair processes mediated in part by the ESCRT-III machinery (Raab et al., 2016). The compromised function of this machinery can result in persistent chromatin exposure, micronuclei formation, and increased mutational load. Repeated rupture–repair cycles therefore provide a mechanistic link between nuclear mechanics and tumor evolution. Recent advances in nuclear mechanobiology further establish the nucleus as a mechanosensitive organelle that integrates cytoskeletal forces with chromatin organization (Stephens et al., 2019). More recently, emerging evidence further positions the NE as an active driver of tumor progression, showing that alterations in NE composition reshape nuclear mechanics and promote malignant transformation rather than serving solely as a diagnostic marker (Paganelli et al., 2025).

Beyond structural disruption, NE instability also bears signaling consequences. Chromatin exposure to the cytoplasm can trigger innate immune sensors such as cGAS, triggering cGAS–STING–dependent inflammatory signaling (Mackenzie et al., 2017), promoting epithelial–mesenchymal transition (EMT) and therapy resistance (Yonesaka et al., 2025). These findings indicate that NE rupture is not only a structural failure but also a driver of inflammatory signaling that may influence therapy response and immune surveillance.

Furthermore, nuclear organization shifts can have a major effect on DNA stability and gene expression (Bickmore and van Steensel, 2013; Burke and Stewart, 2013). In particular, lamina-associated domains (LADs) represent large chromatin regions tethered to the nuclear periphery, contributing to transcriptional repression and genome organization (Van Steensel and Belmont, 2017). Within this mechanistic framework, LEM-D proteins are positioned at the interface of nuclear mechanics, chromatin topology, and genome stability. By tethering chromatin to the nuclear lamina, modulating LADs, and contributing to nuclear stiffness, LEM-D proteins may influence both susceptibility to rupture and the efficiency of NE repair mechanisms. The dysregulation of LEM-D proteins could therefore sensitize nuclei to mechanical failure, alter chromatin–lamina interactions, and promote altered signaling that supports EMT, genome instability, and therapy resistance (Figure 4). This review further delves into the implications of the LEM-D proteins in the context of cancer and highlights the therapeutic potential of such proteins for anti-cancer therapy. Table 1 summarizes LEM-D protein alterations and clinical associations in cancer.

FIGURE 4

3 The functional role of LEM-D proteins in cancer

3.1 LAP2 (TMPO)

The mammalian LAP2 gene also referred to as thymopoietin (TMPO), encodes six splice isoforms (α, β, γ, δ, ε, ζ), all of which share a common ∼180 aa long N-terminal domain that includes an additional LEM-like motif in the N-terminus (Figure 5). The most well-understood isoforms are LAP2α and LAP2β. Nucleoplasmic LAP2α interacts with A-type lamins in the nuclear interior as part of a nucleoskeletal structure (Dechat et al., 1998; Dechat et al., 2000) while LAP2β interacts with B-type lamins at the nuclear periphery (Foisner and Gerace, 1993; Furukawa et al., 1998). The TMPO locus has also been found to be differentially expressed in the prostate (LaTulippe et al., 2002), colon (Agrawal et al., 2002) and central nervous system and embryonal tumors (Pomeroy et al., 2002; Yokota et al., 2004). The nucleoplasmic LAP2α has been reported to either repress or promote proliferation depending on the cellular context (Brachner et al., 2014; Vural et al., 2018). Several studies have demonstrated that LAP2α is mostly expressed in proliferating cells and is downregulated upon cell cycle exit and differentiation (Gotic et al., 2010; Markiewicz et al., 2002; Markiewicz et al., 2005; Naetar et al., 2008). Malignant hematologic disorders (Somech et al., 2007), digestive tract carcinomas (Kim et al., 2012), glioblastoma (Zhang et al., 2016), and various malignancies (Brachner et al., 2014) have all been associated with upregulation of LAP2α and LAP2β (Liu et al., 2019). Clinical studies have reported LAP2α overexpression as an adverse clinicopathologic and independent prognostic marker in gastric cancer (Sun et al., 2019).

FIGURE 5

Dechat et al., 2000).

Early microarray analysis of the LAP2 promoter indicated regulation by E2F1, E2F2, E2F3, p16, and retinoblastoma protein (pRb) (Müller et al., 2001; Vernell et al., 2003). Building on these finding, Parise et al. (2016) examined LAP2α expression in human tumors using tissue microarray analysis and its upregulation in significant cases of primary larynx, lung, stomach, colon and breast cancer tissues. Chromatin immunoprecipitation (ChIP) assays further demonstrated that E2F transcription factors directly regulate the LAP2 promoter, and LAP2α overexpression correlated with tumor proliferation rate in primary tumors (Parise et al., 2006). Consistently, LAP2α expression in cervical cancer was also reported to be linked to E2F-mediated regulation (Ward et al., 2011), reinforcing the connection between the LAP2α-pRb-E2F axis. Notably, as a tumor suppressor and cell cycle regulator, pRb interacts with LAP2α through its C-terminus (Markiewicz et al., 2002; Naetar et al., 2008; Dorner et al., 2006) and LAP2α has been suggested to modulate pRb location and repressor activity in cancer contexts (Markiewicz et al., 2006). Extending these observations to clinical outcome data, Liu and colleagues (Liu et al., 2019) used lung cancer clinical microarray datasets to evaluate the prognostic significance of LAP2α. They report that LAP2α is highly expressed in lung cancer tissues, with elevated levels correlating with unfavorable prognosis. The suppression of LAP2α in lung cancer cells resulted in the inhibition of cell proliferation and the induction of apoptosis. Additionally, reduced LAP2α levels were associated with decreased metastatic potential in tumor cells. Utilizing a mice tumor model, they reported that LAP2α knockdown effectively hinders tumor development in-vivo. These findings suggest that LAP2α may function as a context-dependent oncogenic regulator and potential prognostic marker in lung cancer (Liu et al., 2019). In a previous study, LAP2 knockdown has been shown to suppress proliferation and induce apoptosis, although isoform-specific contributions were not resolved (Zhang et al., 2016).

Interestingly, recent mechanistic work (Wang et al., 2024) has implicated LAP2α in telomere biology where LAP2α suppresses alternative lengthening of telomeres (ALT) by regulating telomeric heterochromatin via interaction with HDAC1. In ALT-positive osteosarcoma models, methotrexate curbed tumor growth, particularly in tumors with low LAP2α expression. This suggests that beyong cell-cycle regulation, LAP2α also controls telomere stability and may influence therapeutic sensitivity in ALT-dependent tumors.

The possible relevance of other LAP2 isoforms in cancer has also been explored in a few studies. LAP2ß, the largest membrane-bound LAP2 isoform, has been reported to be upregulated in various digestive tract cancers, namely, stomach, liver, bile duct and pancreatic cancer. LAP2ß knockdown in pancreatic cancer cells reduced cell motility while its ectopic expression showed the opposite effect (Kim et al., 2012). LAP2ß expression is elevated in the rapidly dividing cells of different hematological malignancies, while it is normally expressed in the slowly dividing cells associated with chronic malignant hematological disorders (Somech et al., 2007). Isoform-selective diagnostic associations have also been reported for LAP2β and γ isoforms in breast and cervical cancer samples, suggesting potential diagnostic value for specific isoforms (Marrero-Rodríguez et al., 2015). Similarly, Huerta-Padilla et al. (2025) reported LAP2 overexpression in cervical cancer, with increased expression of LAP2α,β, and γ in HPV-positive cervical (Huerta-Padilla et al., 2025) and LAP2 (not isoform-resolved) overexpression in papillary thyroid carcinoma (PTC) with predominant cytoplasmic/nuclear-membrane localization. LAP2 knockout inhibited proliferation in PTC cell lines, supporting its candidacy as a biomarker and potential therapeutic target in PTC (Song et al., 2025).

In sum, TMPO/LAP2 is often elevated across cancers, yet some evidence is transcript-based and not isoform-resolved; this distinction is critical given that LAP2α lacks a transmembrane domain and localizes to the nucleoplasm, enabling interaction with A-type lamins and the pRb–E2F cell-cycle axis, whereas membrane-bound LAP2β is anchored at the inner nuclear membrane and more closely associated with motility and EMT-related phenotypes (Figure 5). Preclinical findings indicate that upregulated LAP2 often marks proliferative drive rather than a standalone oncogenic program. However, emerging isoform-resolved studies suggest that isoform context may be particularly relevant for biomarker categorization and for defining targetable vulnerabilities in select tumor settings (Huerta-Padilla et al., 2025; Song et al., 2025; Sun et al., 2019; Wang et al., 2024; Marrero-Rodríguez et al., 2015).

3.2 Emerin (EMD)

Emerin is ubiquitously expressed (Holask et al., 2002; Manilal et al., 1996; Nagano et al., 1996) given its role in diverse biological functions such as transcription regulation, nuclear structure and nucleocytoskeletal mechanics, chromatin compaction, genomic organization, epigenetic modification, and cell signaling (Liddane and Holaska, 2021). A marked reduction in emerin expression has been observed in cases of triple-negative breast cancer (TNBC) (Dittmer and Misteli, 2011), and breast cancer prognosis has been reported to inversely correlate with emerin levels, with lower expression associated with reduced survival (Liddane et al., 2021). Decreased emerin expression has also been associated with enhanced migration, metastasis, and altered nuclear mechanics (Rowat et al., 2006; Lammerding et al., 2005); suggesting a role in maintaining nuclear rigidity and limiting metastatic behavior (Liddane and Holaska, 2021; Liddane et al., 2021).

Emerin depletion or mutation has also been associated with hyperactivation of Mitogen-Activated Protein Kinase (MAPK) signalling (ERK1/2), JNK, p38) MAPK (Bell and Lammerding, 2016; Collins et al., 2017; Iyer et al., 2017; Muchir et al., 2007; Muchir et al., 2008; Muchir et al., 2009), although the precise molecular mechanisms remain to be elucidated. Loss of emerin has also been associated with increased metastatic risk in breast and prostate cancer models (Reis-So et al., 2018; Hu et al., 2011; Wozniak et al., 2013). In ovarian epithelial cancer, emerin and lamin A expression correlate with subtype-specific survival patterns (Watabe et al., 2021). In breast cancer models, Hansen et al. (2024) reported that emerin deficiency promoted invasive transformation, with smaller and misshapen nuclei and an inverse correlation between emerin expression and tumor invasiveness in patient samples (Hansen et al., 2024). In contrast, in KRAS-driven pancreatic ductal adenocarcinoma, increased emerin expression was associated with reduced nuclear size and tumor progression, suggesting context-dependent regulation of nuclear dynamics in PDAC (Flores et al., 2025).

Emerin has been suggested to play an indirect role in tumorigenesis through its interactions with transcription regulators such as GCL (Holaska et al., 2003) and Lim Domain Only Protein 7 (Lmo7) (Holaska et al., 2006). GCL represses E2F-DP3 heterodimerization (delaLuna et al., 1999) and emerin downregulation may increase the expression of E2F and DP3 target genes (Holaska et al., 2003; Holaska and Wilson, 2006). Since Rb represses E2F-DP3–regulated genes required for S-phase entry, emerin has been implicated in regulating cell proliferation (Markiewicz et al., 2006). GCL also recruits GAGE proteins to the nuclear envelope in cancer cells, and is overexpressed in numerous malignancies (Gjerstorff et al., 2012; Gjerstorff and Ditzel, 2008).

Emerin binding restricts Lmo7 transcriptional activation (Holaska et al., 2006). Lmo7 overexpression has been reported across multiple cancers (Furuya et al., 2002; Kang et al., 2000; Sasaki et al., 2003). However, its precise role remains context dependent as Lmo7-deficient mice developed irregular epithelial lesions and late-onset lung adenocarcinoma at an older age, indicating that Lmo7 may function as a tumor-suppressor gene (Tanaka-Okamoto et al., 2009).

Emerin has also been been linked to major signaling pathways (Liddane et al., 2021), including Wnt, IGF, TGF-ß, and Notch (Haraguchi et al., 2004), JNK, MAPK (Collins et al., 2017). Emerin directly interacts with ß-catenin and restricts its nuclear accumulation (Markiewicz et al., 2006). Cells lacking emerin exhibit heightened expression of ß-catenin levels and transcriptional activity (Markiewicz et al., 2006; Tilgner et al., 2009). Notably, the suppression of ß-catenin correlates with reduced mRNA expression and nuclear accumulation of emerin (Tilgner et al., 2009), suggesting a reciprocal regulation of expression, localization, and function between emerin and ß-catenin. Wnt activation has been linked to EMT, stem-like cell expansion, immune evasion, and therapy resistance (Rosner et al., 2002; Spranger et al., 2015). Through regulation of nuclear actin dynamics, emerin influences MKL1/SRF signaling (Ho et al., 2013; Miralles et al., 2003), which contributes to EMT and tumor progression (Hirano and Matsuura, 2011; Pawłowski et al., 2010).

Recent studies further extend emerin’s role in cancer biology. For instance, Popęda et al. (2024) showed that emerin mislocalization to micronuclei was linked to increased invasiveness and poorer prognosis in prostate cancer, especially in metastatic tumors with higher Gleason scores (Popęda et al., 2024). Consistently, reduced EMD expression in metastatic castration-resistant prostate cancer has been linked to a very-small-nuclear phenotype in circulating tumor cells, accompanied by lineage plasticity, enhanced invasion, and resistance to androgen receptor–targeted therapies (Zhang et al., 2025).

In short, emerin downregulation is associated with worsened survival and increased migration/metastasis. Emerging evidence in prostate cancer further correlates emerin mislocalization or reduced expression to invasive phenotypes, lineage plasticity, and therapeutic resistance. Emerin contributes to nucleo-cytoskeletal coupling and nuclear mechanics and has been shown to restrain oncogenic signaling by restricting nuclear β-catenin (Wnt/β-catenin) and modulating MKL1/SRF and MAPK pathways. Clinically, evidence is strongest in breast and prostate cancers but remains heterogeneous and lineage-dependent (with potential lamin A/C confounding). Therapeutic strategies targeting Wnt/β-catenin, hyperactive MAPK activity, or plasticity programs in the context of emerin loss warrant further investigation.

3.3 LEMD1

LEMD1 belongs to the cancer/testis antigen (CTA) gene family (Yuki et al., 2004), which is typically expressed in normal testis and malignant tissues (Chang et al., 2019). CTAs have been associated with dysregulation in multiple cancers and have been proposed as potential tumor markers for screening, prognosis, disease progression, and therapeutic interventions (Li et al., 2017; Salmaninejad et al., 2016). Elevated CTA expression correlates with advanced disease and poorer survival outcomes (Salmaninejad et al., 2016; Mooney et al., 2016; Yang et al., 2015). LEMD1 was initially identified as overexpressed in colorectal tumors (Yuki et al., 2004), prostate cancer (Ghafouri-Fard et al., 2010), and lymphoma cells (Matsuyama et al., 2011).

Recently, Cao and colleagues (Cao et al., 2022) reported evidence supporting a potential oncogenic role for LEMD1 in pancreatic cancer. LEMD1 was upregulated and negatively associated with overall and disease-free survival rates. Functional studies showed that LEMD1 suppression reduced proliferation, migration, and invasion; whereas overexpression was associated with increased tumor aggressiveness. Gene Set Enrichment Analysis (GSEA) suggested that LEMD1 may contribute to pancreatic cancer progression via p53 repression and mTORC1 activation (Cao et al., 2022).

LEMD1 has also been implicated in prostate, oral squamous cell carcinoma, gastric, and colorectal cancers (Li et al., 2019; Sasahira et al., 2016; Yuki et al., 2004; Ghafouri-Fard et al., 2010). In thyroid cancer, LEMD1 depletion inhibited cell proliferation and migration and triggered apoptosis by suppressing EMT and Wnt/ß-catenin signaling (Xu et al., 2021). Elevated LEMD1 expression has been associated with lymph node metastasis and a dismal prognosis in oral squamous cell carcinoma (Sasahira et al., 2016; Sasahira et al., 2020). In colorectal cancer, LEMD1 upregulation correlates with poorer survival (Martinez-Romero et al., 2018), although the underlying regulatory mechanisms remain unclear.

SRY-related high-mobility-group box 4 (SOX4), a frequently overexpressed transcription factor in various malignant tumors (Hanieh et al., 2020) has been proposed as a regulator of LEMD1 expression. A recent study reported that SOX4 binds the LEMD1 promoter and that LEMD1 activation was associated with increased PI3K/AKT signaling in colon cancer (Li et al., 2022a), gastric and colorectal cancer (Li et al., 2019; Luo et al., 2021) and in various other cancer malignancies (Narayan and ankutty, 2019; Pal and Mandal, 2012; Ponnurangam et al., 2013). Recent data further reinforces PI3K/AKT pathway involvement in non-small cell lung cancer, where LEMD1 overexpression correlated with advanced stage and poorer survival and promoted malignant stemness and invasion (Li and Zhang, 2024). Additional studies indicate that LEMD1 may influence colorectal cancer stemness and motility (Takeda et al., 2017). More recently, LEMD1 was shown to promote migration in colorectal cancer through the RhoA/ROCK signaling pathway; inhibition of RhoA/ROCK attenuated LEMD1-dependent motility (Zhan et al., 2022).

In TNBC, LEMD1 was reported to be upregulated, and its silencing inhibited proliferation and migration in-vitro and suppressed tumor development in-vivo (Li et al., 2023). LEMD1 has been reported to regulate TNBC progression via ERK signaling, and its inhibition enhanced chemosensitivity. A pan-cancer analysis further demonstrated LEMD1 upregulation across multiple malignancies, with high expression associated with poorer overall survival in pancreatic adenocarcinoma, kidney renal papillary cell carcinoma, colon adenocarcinoma, and kidney renal clear cell carcinoma. Emerging evidence suggests that LEMD1 expression is regulated by the antisense lncRNA LEMD1-AS1. In OSCC, LEMD1-AS1 upregulation stabilized LEMD1 transcripts and activated PI3K/AKT signaling, enhancing metastasis (Li et al., 2022b). Conversely, reduced LEMD1-AS1 expression in epithelial ovarian cancer was associated with poorer survival, suggesting context-dependent regulation of the LEMD1 axis (Yang et al., 2022).

Overall, LEMD1 is frequently elevated across multiple cancers, and its silencing in TNBC limits tumor growth and heightens chemosensitivity, supporting a biological rationale for its potential role as a prognostic and predictive biomarker in TNBC. Functional studies suggest that LEMD1 promotes tumor progression through PI3K/AKT, ERK, and RhoA/ROCK signaling, contributing to EMT, stemness, and motility. Recent report of lncRNA-mediated regulation (e.g., LEMD1-AS1) further supports this oncogenic axis.

3.4 LEMD2

LEMD2 mediates chromatin-NE interactions (Brachner et al., 2005; Huber et al., 2009; Ulbert et al., 2006) and is required for NE reformation following cell division, as well as for maintaining nuclear integrity and chromatin stabilization (Vietri et al., 2020; Von Appen et al., 2020). LEMD2, together with ANKLE1 and EMD, has been reported to correlate with advanced tumor stage and survival prognosis in prostate adenocarcinoma (PRAD). Consistent with computational analysis, mRNA and protein expression levels of these genes were markedly increased in PRAD, and their expression was associated with immune cell infiltration. DNA methylation or/and copy number variations have been proposed to contribute to the upregulation of these LEM-D proteins in PRAD (He et al., 2022).

Given the frequent dysregulation of NE proteins in cancer cells, a recent study (Rose et al., 2024) evaluated the association between LEM-D proteins and TNBC. Using publicly available data, they studied the expression and prognostic implications of ANKLE2, LAP2, emerin, and LEMD2. siRNA-mediated depletion of individual LEM-D proteins was followed by proliferation and apoptosis assays. LEM-D transcripts were generally upregulated in patient samples; although protein levels were variable in TNBC cell lines and inversely associated with survival. Depletion of LEM-D proteins induced abnormal nuclear morphology, reduced proliferation, and cell death, whereas minimal effects were observed in non-cancerous cells. While these findings support an association between Ankle2, TMPO, emerin, and LEMD2 expression and TNBC, a larger cohort is needed for confirmation.

In sum, LEMD2 preserves nuclear integrity by anchoring chromatin to the NE. LEMD2 is associated with higher stage, poorer survival, and immune cell infiltration in prostate adenocarcinoma. In TNBC, transcripts levels trend upwards, whereas protein levels vary; siRNA knockdown selectively perturbs cancer nuclear morphology and proliferation, implying dependence. Therapeutic approaches targeting NE-stress or DNA damage response DDR vulnerabilities remain exploratory and warrant further investigation in LEMD2-high tumors.

3.5 MAN1 (LEMD3)

MAN1/LEMD3 is the longest member of the LEM family. A significant part of its role is attributed to its interaction with R-SMADs (Osada et al., 2003). The R-SMAD proteins play a crucial role as regulators of numerous signaling pathways. In addition to its role in transcriptional regulation, LEMD3 also contributes to NE organization during the cell cycle (Yam et al., 2013). It has also been reported to activate the BMAL1 promoter, a core “clock gene” that orchestrates the circadian rhythm (Lin et al., 2014).

LEMD3 counteracts TGFβ/BMP signaling (Lin et al., 2005; Osada et al., 2003) by binding R-SMADs. Since TGFβ/BMP is growth-suppressive at early stages but pro-EMT/pro-metastatic in advanced disease, LEMD3’s effect may be context-dependent, potentially modulating stage-specific signaling effects.

Although LEMD3 is not well studied as a cancer gene, recurrent mutations have been identified in specific gliomas. Assessing the impact of infrequent variants on progression is challenging. Masica and Karchin highlighted low-frequency mutated genes in The Cancer Genome Atlas (TCGA) glioblastoma (GBM) cohort. Notably, ATM, KLF6, and LEMD3 were among the mutations with low frequency in TCGA GBM tumor samples, showing complete co-mutation overlap. These mutations are strongly associated with significant altered expression of 165 additional genes, suggesting a potential cooperative role in tumorigenesis within select TCGA GBM samples (Masica and Karchin, 2011). In non-small cell lung cancer, pharmacogenetic analyses have linked LEMD3 expression and specific SNP-associated eQTL signals with overall survival in non-smokers (Stewart et al., 2014). Large-scale multi-omic analyses of colorectal cancer further identified LEMD3 among genes associated with CRC susceptibility, suggesting involvement of TGFβ-related pathways; although functional validation remains limited (Fernandez-Rozadilla et al., 2023). Provide the complete details for reference “Pamer, 2016”. https://www.frontiersin.org.cn/authors-proof-support/#QA49

LEMD3 is most notable for its implication in osteopoikilosis (OPK) and Buschke-Ollendorff syndrome (BOS). The identification of heterozygous, loss-of-function, germline mutations in the LEMD3 gene has shed light on the etiology of both OPK and BOS (Hellemans et al., 2004). OPK, a rare benign bone disorder, manifests as asymptomatic dense bone lesions that resemble bone metastasis. These mutations can arise sporadically or via autosomal dominant inheritance (Gutierrez et al., 2015). BOS is characterized by OPK along with connective-tissue nevi/juvenile elastomas, resulting in soft-tissue and skin lesions (Zhang et al., 2009). Subsequent research confirmed and expanded the spectrum of loss-of-function LEMD defects (Hellemans et al., 2006; Mumm et al., 2007). Genetic diversity has also been reported (Yadegari et al., 2010).

Although no direct link between OPK and cancer predisposition has been established, an interesting case involved a patient with an LEMD3 germline mutation and a heterozygous somatic KRAS mutation in a skin nevus. The potential facilitation of postzygotic mosaicism of mutated KRAS by germline LEMD3 haploinsufficiency remains uncertain (Hellemans et al., 2004). Recently, Correa Llano and colleagues reported a case of a patient diagnosed with a mixed germ cell tumor and OPK who achieved complete remission following chemotherapy and surgery (Correa et al., 2020). Consistent with its role as a TGFβ pathway antagonist, LEMD3 has recently been implicated in tumor microenvironment signaling. In gastric cancer, exosomal miR-21-5p was shown to target LEMD3 in endothelial cells, resulting in activation of TGFβ/Smad signaling and elevated VEGFA expression, thereby promoting angiogenesis (Zhou and Lu, 2024).

In brief, evidence for the prognostic value of MAN1/LEMD3 in cancer remains limited. Emerging studies suggest that LEMD3 may influence tumor biology through modulation of TGFβ/BMP signaling, angiogenesis, and genetic susceptibility pathways, but these associations are largely context-dependent and require further mechanistic validation. While germline loss-of-function mutations in LEMD3 underlie OPK/BOS syndromes, a definitive link to cancer predisposition has not been established.

3.6 ANKLE1

ANKLE1 was initially considered an endonuclease (Brachner et al., 2012). It mediates mitochondrial DNA cleavage and is involved in DNA damage response and repair mechanisms.

Given that many breast cancer-predisposition genes are involved in DNA repair pathways (e.g., BRCA1, BRCA2, Rad51, Chek2, ATM, p53), ANKLE1 has been proposed as a candidate sesceptibility gene (Brachner et al., 2014). Genomic analyses identified single nucleotide polymorphisms (SNPs) at chromosomal locus 19p13.11 siginificantly associated with breast cancer susceptibility (Antoni et al., 2010; Stevens et al., 2011; Bolton et al., 2010; Chen et al., 2011; Zhang et al., 2011). Subsequent studies reported associations between ANKLE1 variants and breast (Stevens et al., 2011) and ovarian cancer risk (Lawrenson et al., 2016). However, integrative GWAS and eQTL analyses suggests that ABHD8, rather than ANKLE1, may represent the primary causal gene at this locus (Lawrenson et al., 2016), although ANKLE1 expression may be influenced by regulatory variants affecting transcription factor binding (Liu et al., 2017). Whole-exome sequencing and genotyping studies in breast cancer cohorts from an Indian population further suggested that ANKLE1 variation may influence DNA repair efficiency. In MCF-7 cells, ANKLE1 depletion increased DNA damage and nuclear localization was observed following genotoxic stress (Bakshi et al., 2021), supporting a role in genome maintenance.

Mechanistically, elevated ANKLE1 has been reported to induce mtDNA cleavage, triggering mitophagy and a metabolic shift toward glycolysis, favoring cancer cell survival and proliferation. mtDNA degradation has also been associated with STAT1 activation and induction of EMT-related genes. In TP53-mutant contexts, ANKLE1 has been shown to cleave nuclear DNA without inducing apoptosis, potentially increasing mutational burden (Przanowski et al., 2023). These findings suggest that ANKLE1 overexpression may contribute to genomic instability and tumor progression in certain cases. Conversely, an m6A-associated variant (rs8100241) within ANKLE1 has been linked to reduced colorectal cancer (CRC) risk through increased m6A modification and elevated ANKLE1 expression (Tian et al., 2020). In CRC, ANKLE1 appears to act as a tumor suppressor by preserving genomic stability, and lower expression has been reported in tumor tissues relative to normal samples. Subsequent work has further connected ANKLE1 to m6A-dependent regulation, showing that METTL3-mediated methylation enhances ANKLE1 mRNA stability and protein expression, contributing to reduced CRC risk (Li et al., 2021). These findings underscore lineage-dependent effects, with ANKLE1 exhibiting oncogenic features in breast/TNBC models but tumor-suppressive associations in CRC. ANKLE1 has also been incorporated into prognostic gene signatures in lung squamous cell carcinoma (Jiang et al., 2022) and colon cancer (Kang et al., 2022), although functional validation remains limited.

More recently, ANKLE1 has been shown to localize to the midbody and resolve chromatin bridges during cytokinesis, thereby preventing micronuclei formation and limiting activation of the cGAS–STING pathway (Jiang et al., 2023). ANKLE1 knockout resulted in increased DNA damage, prolonged DNA damage response signaling, and replication stress, further supporting its role in genome stability maintenance.

In summary, ANKLE1 at locus 19p13.1 is associated with cancer susceptibility and DNA damage responses. Evidence suggests context-dependent roles whereby elevated expression may promote genomic instability in breast/TNBC models, while increased expression in CRC may correlate with reduced cancer risk.

3.7 LEM4 (ANKLE2)

Unlike ANKLE1, which functions as an endonuclease, ANKLE2 serves as a scaffold facilitating various protein-protein interactions and is involved in maintaining NE stability. In high-grade serous ovarian carcinoma, ANKLE2 is among a group of 12 genes that engage with VIRMA, a gene that enhances tumor aggressiveness through N6-methylation of adenosine (m6A) (Miranda-Gonçalves et al., 2021). Suppression of ANKLE2 through RNA interference in different human ovarian cancer cell lines (SKOV3, OVCAR, and APOCC) reduced viability and migration, and heightened sensitivity to paclitaxel (Al-Farsi et al., 2022). Similarly, in estrogen receptor-positive (ESR+) human breast cancer cell lines, overexpression of ANKLE2 has been associated with enhanced tumor progression. Mechanistically, ANKLE2 supports the phosphorylation of the tumor suppressor protein Rb and activation the cyclin D-CDK4-Rb; and is associated with tamoxifen resistance (Gao et al., 2018). In ESR + human breast cancer cells, ANKLE2 acts as a scaffold promoting estrogen receptor alpha (ESRα) phosphorylation through aurora-A kinase, thereby activating Erα transcriptional activity. More recently, Tang et al. (2025) reported that ANKLE2 upregulation is associated with acquired resistance to the CDK4/6 inhibitor ribociclib in breast cancer models. ANKLE2 was shown to stabilize β-catenin, increasing its protein stability, nuclear translocation, and transcriptional activity. Silencing ANKLE2 restored ribociclib sensitivity in resistant cells, and pharmacologic inhibition of β-catenin signaling reversed this resistance phenotype. These findings suggest that ANKLE2 may contribute to CDK4/6 inhibitor resistance through modulation of β-catenin signaling (Tang et al., 2025). Overall, ANKLE2 dysregulation has been linked to tumor growth and therapy resistance in high-grade serous ovarian carcinoma and in breast cancer models. Figure 6 below summarizes the signaling pathways and cancer phenotypes driven by LEM-D proteins.

FIGURE 6

4 Latest progress in therapeutic targeting of LEM-D proteins for cancer treatment

At present, there is no FDA-approved agents that directly target LEM-D proteins. Current strategies primarily involve indirect pharmacologic targeting of downstream signaling pathways and gene-silencing techniques.

Preclinical gene-targeting strategies provide proof-of-concept evidence that LEM-D proteins are functionally targetable. 1n TNBC, siRNA-mediated depletion of EMD, ANKLE2, TMPO, and LEMD2 significantly reduced proliferation and induced apoptosis, while exerting minimal effects on non-malignant cells (Rose et al., 2024). Similarly, RNA interference–mediated suppression of ANKLE2 in ovarian cancer reduced migration and enhanced paclitaxel sensitivity (Al-Farsi et al., 2022). In pancreatic cancer, LEMD1 knockdown inhibited proliferation and invasion while suppressing mTORC1 activation and restoring apoptotic signaling (Cao et al., 2022). In TNBC models, LEMD1 depletion reduced tumor growth and enhanced chemotherapy sensitivity through ERK pathway inhibition (Li et al., 2023).

At present, direct small-molecule inhibitors targeting LEM-D proteins are lacking. However, several studies demonstrate that LEM-D–mediated therapeutic resistance can be pharmacologically reversed by targeting downstream pathways. In ER-positive breast cancer, ANKLE2-mediated tamoxifen resistance was reversed using the CDK4/6 inhibitor palbociclib (Gao et al., 2018). More recently, Tang et al. showed that ANKLE2-mediated ribociclib resistance is mediated through β-catenin stabilization, and pharmacologic β-catenin inhibition restored drug sensitivity (Tang et al., 2025). While other pathway dependencies such as PI3K/AKT activation in LEMD1-high tumors or MAPK/β-catenin signaling in emerin-deficient cancers suggest rational combination strategies, these remain prospective and have not yet been clinically validated.

5 Concluding remarks and future perspectives

LEM-D proteins play a central role in nuclear architecture, chromatin organization, and oncogenic signaling, and their dysregulation is increasingly associated with tumor progression and therapeutic resistance. Yet, direct pharmacologic inhibition of LEM-D proteins has not yet been realized. Instead, translational efforts have focused on indirect targeting strategies. Insights from laminopathies indicate that NE dysfunction impairs DNA repair capacity (Bolderson et al., 2019; Gonzalo and Kreienkamp, 2015), supporting potential combination strategies with DNA damage response inhibitors. Additionally, nuclear export inhibition has shown anti-cancer activity in selected malignancies (Shao et al., 2011), although such approaches have not been specifically adopted for LEM-D associated tumors. Much of the current evidence linking LEM-D proteins to cancer is drawn from transcript-level datasets and in-vitro models, with limited isoform-specific resolution and insufficiently validated antibodies for precise protein-level and spatial analysis. Additionally, subnuclear localization dynamics and mechanobiological behavior in patient-derived tissues remain underexplored, and in-vivo functional validation is limited across tumor types. Addressing these gaps will require integration of proteomic tools, high-resolution imaging, mechanobiology approaches, and lineage-specific in vivo models to clarify context-dependent roles of LEM-D proteins in cancer.

Future progress will require better validation of LEM-D proteins at the protein level and more carefully designed clinical studies that take LEM-D protein expression into account.

References

• 1

  AgrawalD.ChenT.IrbyR.QuackenbushJ.ChambersA. F.SzaboM.et al (2002). Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling. J. Natl. Cancer Inst.94, 513–521. 10.1093/jnci/94.7.513

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 2

  Al-FarsiH.Al-AzwaniI.MalekJ. A.ChouchaneL.RafiiA.HalabiN. M. (2022). Discovery of new therapeutic targets in ovarian cancer through identifying significantly non-mutated genes. J. Transl. Med.20, 244. 10.1186/s12967-022-03440-5

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 3

  AntoniouA. C.WangX.FredericksenZ. S.McGuffogL.TarrellR.SinilnikovaO. M.et al (2010). A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population. Nat. Genet.42, 885–892. 10.1038/ng.669

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 4

  BakhoumS. F.NgoB.LaughneyA. M.CavalloJ.-A.MurphyC. J.LyP.et al (2018). Chromosomal instability drives metastasis through a cytosolic DNA response. Nature553, 467–472. 10.1038/nature25432

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 5

  BakshiD.KatochA.ChakrabortyS.ShahR.SharmaB.BhatA.et al (2021). ANKLE1 as new hotspot mutation for breast cancer in Indian population and has a role in DNA damage and repair in Mammalian cells. Front. Genet.11, 609758. 10.3389/fgene.2020.609758

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 6

  BellE. S.LammerdingJ. (2016). Causes and consequences of nuclear envelope alterations in tumour progression. Eur. J. Cell Biol.95, 449–464. 10.1016/j.ejcb.2016.06.007

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 7

  BickmoreW. A.van SteenselB. (2013). Genome architecture: domain organization of interphase chromosomes. Cell152, 1270–1284. 10.1016/j.cell.2013.02.001

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 8

  BoldersonE.BurgessJ. T.LiJ.GandhiN. S.BoucherD.CroftL. V.et al (2019). Barrier-to-autointegration factor 1 (Banf1) regulates poly [ADP-ribose] polymerase 1 (PARP1) activity following oxidative DNA damage. Nat. Commun.10, 5501. 10.1038/s41467-019-13167-5

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 9

  BoltonK. L.TyrerJ.SongH.RamusS. J.NotaridouM.JonesC.et al (2010). Common variants at 19p13 are associated with susceptibility to ovarian cancer. Nat. Genet.42, 880–884. 10.1038/ng.666

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 10

  BrachnerA.FoisnerR. (2011). Evolvement of LEM proteins as chromatin tethers at the nuclear periphery. Biochem. Soc. Trans.39, 1735–1741. 10.1042/BST20110724

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 11

  BrachnerA.ReipertS.FoisnerR.GotzmannJ. (2005). LEM2 is a novel MAN1-related inner nuclear membrane protein associated with A-type lamins. J. Cell Sci.118, 5797–5810. 10.1242/jcs.02701

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 12

  BrachnerA.BraunJ.GhodgaonkarM.CastorD.ZlopasaL.EhrlichV.et al (2012). The endonuclease Ankle1 requires its LEM and GIY-YIG motifs for DNA cleavage in vivo. J. Cell Sci.125, 1048–1057. 10.1242/jcs.098392

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 13

  BrachnerA.FoisnerR. (2014). “Lamina-Associated polypeptide (LAP)2α and other LEM proteins in cancer biology,” in Cancer biology and the nuclear envelope. Advances in experimental medicine and biology. Editors SchirmerE. C.De Las HerasJ. I. (New York, NY: Springer New York), 143–163. 10.1007/978-1-4899-8032-8_7

  • CrossRef
  • Google Scholar
  • View reference in article

• 14

  BurkeB.StewartC. L. (2013). The nuclear lamins: flexibility in function. Nat. Rev. Mol. Cell Biol.14, 13–24. 10.1038/nrm3488

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 15

  CaiM.HuangY.GhirlandoR.WilsonK. L.CraigieR.CloreG. M. (2001). Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: one binds BAF and the other binds DNA. EMBO J.20, 4399–4407. 10.1093/emboj/20.16.4399

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 16

  CaoX.YaoN.ZhaoZ.FuY.HuY.ZhuP.et al (2022). LEM domain containing 1 promotes pancreatic cancer growth and metastasis by p53 and mTORC1 signaling pathway. Bioengineered13, 7771–7784. 10.1080/21655979.2022.2047404

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 17

  CaputoS.CouprieJ.Duband-GouletI.KondéE.LinF.BraudS.et al (2006). The carboxyl-terminal nucleoplasmic Region of MAN1 exhibits a DNA binding winged helix domain. J. Biol. Chem.281, 18208–18215. 10.1074/jbc.M601980200

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 18

  ChangY.WangX.XuY.YangL.QianQ.JuS.et al (2019). Comprehensive characterization of cancer-testis genes in testicular germ cell tumor. Cancer Med.8, 3511–3519. 10.1002/cam4.2223

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 19

  ChenF.ChenG. K.MillikanR. C.JohnE. M.AmbrosoneC. B.BernsteinL.et al (2011). Fine-mapping of breast cancer susceptibility loci characterizes genetic risk in African Americans. Hum. Mol. Genet.20, 4491–4503. 10.1093/hmg/ddr367

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 20

  CollinsC. M.EllisJ.HolaskaJ. M. (2017). MAPK signaling pathways and HDAC3 activity are disrupted during emerin-null myogenic progenitor differentiation. Dis. Models and Mech., 10 (4), 385–397. 10.1242/dmm.028787

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 21

  CorreaL. M. G.MoraJ.TornerF.InarejosE.CruzO. (2020). Osteopoikilosis with germline LEMD3 Mutation mimicking bone metastases in a girl with a concurrent secreting mixed germ cell tumor. J. Pediatr. Hematol. Oncol.42, e185–e187. 10.1097/MPH.0000000000001457

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 22

  DechatT.GotzmannJ.StockingerA.HarrisC. A.TalleM. A.SiekierkaJ. J.et al (1998). Detergent-salt resistance of LAP2alpha in interphase nuclei and phosphorylation-dependent association with chromosomes early in nuclear assembly implies functions in nuclear structure dynamics. EMBO J.17, 4887–4902. 10.1093/emboj/17.16.4887

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 23

  DechatT.KorbeiB.VaughanO. A.VlcekS.HutchisonC. J.FoisnerR. (2000). Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins. J. Cell Sci.113 (9), 3473–3484. 10.1242/jcs.113.19.3473

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 24

  DedeicZ.CeteraM.CohenT. V.HolaskaJ. M. (2011). Emerin inhibits Lmo7 binding to the Pax3 and MyoD promoters and expression of myoblast proliferation genes. J. Cell Sci.124, 1691–1702. 10.1242/jcs.080259

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 25

  delaLunaS.AllenK. E.MasonS. L.La ThangueN. B. (1999). Integration of a growth-suppressing BTB/POZ domain protein with the DP component of the E2F transcription factor. EMBO J.18, 212–228. 10.1093/emboj/18.1.212

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 26

  DemmerleJ.KochA. J.HolaskaJ. M. (2012). The nuclear envelope protein emerin binds directly to histone deacetylase 3 (HDAC3) and activates HDAC3 activity. J. Biol. Chem.287, 22080–22088. 10.1074/jbc.M111.325308

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 27

  DenaisC.LammerdingJ. (2014). Nuclear mechanics in cancer. Adv. Exp. Med. Biol.773, 435–470. 10.1007/978-1-4899-8032-8_20

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 28

  DenaisC. M.GilbertR. M.IsermannP.McGregorA. L.Te LindertM.WeigelinB.et al (2016). Nuclear envelope rupture and repair during cancer cell migration. Science352, 353–358. 10.1126/science.aad7297

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 29

  DittmerT. A.MisteliT. (2011). The lamin protein family. Genome Biol.12, 222. 10.1186/gb-2011-12-5-222

  • Pubmed Abstract
  • CrossRef
  • Google Scholar
  • View reference in article

• 30

  DornerD.VlcekS.FoegerN.GajewskiA.MakolmC.GotzmannJ.et al (2006). Lamina-associated polypeptide 2alpha regulates cell cycle progression and differentiation via the retinoblastoma-E2F pathway. J. Cell Biol.173, 83–93. 10.1083/jcb.200511149

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 31

  Fernandez-RozadillaC.TimofeevaM.ChenZ.LawP.ThomasM.SchmitS.et al (2023). Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries. Nat. Genet.55, 89–99. 10.1038/s41588-022-01222-9

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 32

  FloresL. F.MarksD. L.VeraR. E.SigafoosA. N.TolosaE. J.AlmadaL. L.et al (2025). Emerin is an effector of oncogenic KRAS-driven nuclear dynamics in pancreatic cancer. JCI Insight10, e187799. 10.1172/jci.insight.187799

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 33

  FoisnerR.GeraceL. (1993). Integral membrane proteins of the nuclear envelope interact with lamins and chromosomes, and binding is modulated by mitotic phosphorylation. Cell73, 1267–1279. 10.1016/0092-8674(93)90355-t

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 34

  FriedlP.WolfK.LammerdingJ. (2011). Nuclear mechanics during cell migration. Curr. Opin. Cell Biol.23, 55–64. 10.1016/j.ceb.2010.10.015

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 35

  FurukawaK.FritzeC. E.GeraceL. (1998). The major nuclear envelope targeting domain of LAP2 coincides with its lamin binding region but is distinct from its chromatin interaction domain. J. Biol. Chem.273, 4213–4219. 10.1074/jbc.273.7.4213

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 36

  FuruyaM.TsujiN.EndohT.MoriaiR.KobayashiD.YagihashiA.et al (2002). A novel gene containing PDZ and LIM domains, PCD1, is overexpressed in human colorectal cancer. Anticancer Res.22, 4183–4186.

  • Pubmed Abstract
  • Google Scholar

• 37

  GaoA.SunT.MaG.CaoJ.HuQ.ChenL.et al (2018). LEM4 confers tamoxifen resistance to breast cancer cells by activating cyclin D-CDK4/6-Rb and ERα pathway. Nat. Commun.9, 4180. 10.1038/s41467-018-06309-8

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 38

  Ghafouri-FardS.Ousati AshtianiZ.Sabah GolianB.HasheminasabS.-M.ModarressiM. H. (2010). Expression of two testis-specific genes, SPATA19 and LEMD1. Prostate Cancer41, 195–200. 10.1016/j.arcmed.2010.04.003

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 39

  GjerstorffM. F.DitzelH. J. (2008). An overview of the GAGE cancer/testis antigen family with the inclusion of newly identified members. Tissue Antigens71, 187–192. 10.1111/j.1399-0039.2007.00997.x

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 40

  GjerstorffM. F.RösnerH. I.PedersenC. B.GreveK. B. V.SchmidtS.WilsonK. L.et al (2012). GAGE cancer-germline antigens are recruited to the nuclear envelope by germ cell-less (GCL). PLoS One7, e45819. 10.1371/journal.pone.0045819

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 41

  GonzaloS.KreienkampR. (2015). DNA repair defects and genome instability in Hutchinson–Gilford Progeria Syndrome. Curr. Opin. Cell Biol.34, 75–83. 10.1016/j.ceb.2015.05.007

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 42

  GoticI.SchmidtW. M.BiadasiewiczK.LeschnikM.SpilkaR.BraunJ.et al (2010). Loss of LAP2 alpha delays satellite cell differentiation and affects postnatal fiber-type determination. Stem Cells28, 480–488. 10.1002/stem.292

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 43

  GutierrezD.CooperK. D.MitchellA. L.CohnH. I. (2015). Novel somatic mutation in LEMD3 splice site results in buschke-ollendorff syndrome with polyostotic melorheostosis and osteopoikilosis. Pediatr. Dermatol32, e219–e220. 10.1111/pde.12634

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 44

  HaniehH.AhmedE. A.VishnubalajiR.AlajezN. M. (2020). SOX4: epigenetic regulation and role in tumorigenesis. Semin. Cancer Biol.67, 91–104. 10.1016/j.semcancer.2019.06.022

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 45

  HansenE.RollingC.WangM.HolaskaJ. M. (2024). Emerin deficiency drives MCF7 cells to an invasive phenotype. Sci. Rep.14, 19998. 10.1038/s41598-024-70752-5

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 46

  HaraguchiT.HolaskaJ. M.YamaneM.KoujinT.HashiguchiN.MoriC.et al (2004). Emerin binding to Btf, a death‐promoting transcriptional repressor, is disrupted by a missense mutation that causes Emery–Dreifuss muscular dystrophy. Eur. J. Biochem.271, 1035–1045. 10.1111/j.1432-1033.2004.04007.x

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 47

  HeT.ZhangY.LiX.LiuC.ZhuG.YinX.et al (2022). Collective analysis of the expression and prognosis for LEM-domain proteins in prostate cancer. World J. Surg. Onc20, 174. 10.1186/s12957-022-02640-z

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 48

  HellemansJ.PreobrazhenskaO.WillaertA.DebeerP.VerdonkP. C. M.CostaT.et al (2004). Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. Nat. Genet.36, 1213–1218. 10.1038/ng1453

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 49

  HellemansJ.DebeerP.WrightM.JaneckeA.KjaerK. W.VerdonkP. C. M.et al (2006). Germline LEMD3 mutations are rare in sporadic patients with isolated melorheostosis. Hum. Mutat.27, 290. 10.1002/humu.9403

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 50

  HiranoH.MatsuuraY. (2011). Sensing actin dynamics: structural basis for G-actin-sensitive nuclear import of MAL. Biochem. Biophys. Res. Commun.414, 373–378. 10.1016/j.bbrc.2011.09.079

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 51

  HoC. Y.JaaloukD. E.VartiainenM. K.LammerdingJ. (2013). Lamin A/C and emerin regulate MKL1–SRF activity by modulating actin dynamics. Nature497, 507–511. 10.1038/nature12105

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 52

  HolaskaJ. M.WilsonK. L.MansharamaniM. (2002). The nuclear envelope, lamins and nuclear assembly. Curr. Opin. Cell Biol.14, 357–364. 10.1016/S0955-0674(02)00329-0

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 53

  HolaskaJ. M.WilsonK. L. (2006). Multiple roles for emerin: implications for Emery-Dreifuss muscular dystrophy. Anat. Rec.288A, 676–680. 10.1002/ar.a.20334

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 54

  HolaskaJ. M.LeeK. K.KowalskiA. K.WilsonK. L. (2003). Transcriptional repressor germ cell-less (GCL) and barrier to autointegration factor (BAF) compete for binding to emerin in vitro. J. Biol. Chem.278, 6969–6975. 10.1074/jbc.M208811200

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 55

  HolaskaJ. M.Rais-BahramiS.WilsonK. L. (2006). Lmo7 is an emerin-binding protein that regulates the transcription of emerin and many other muscle-relevant genes. Hum. Mol. Genet.15, 3459–3472. 10.1093/hmg/ddl423

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 56

  HuQ.GuoC.LiY.AronowB. J.ZhangJ. (2011). LMO7 mediates cell-specific activation of the rho-myocardin-related transcription factor-serum response factor pathway and plays an important role in breast cancer cell migration. Mol. Cell. Biol.31, 3223–3240. 10.1128/MCB.01365-10

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 57

  HuberM. D.GuanT.GeraceL. (2009). Overlapping functions of nuclear envelope proteins NET25 (Lem2) and emerin in regulation of extracellular signal-regulated kinase signaling in myoblast differentiation. Mol. Cell Biol.29, 5718–5728. 10.1128/MCB.00270-09

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 58

  Huerta-PadillaV.Marrero-RodríguezD.Taniguchi-PoncianoK.LópezA. E.Candanedo-GonzálezF.SalcedoE.et al (2025). Thymopoietin-α, -β, and -γ isoforms increased expression in cervical cancer cells. Can. J. Infect. Dis. Med. Microbiol.2025, 1668482. 10.1155/cjid/1668482

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 59

  IsermannP.LammerdingJ. (2017). Consequences of a tight squeeze: nuclear envelope rupture and repair. Nucleus8, 268–274. 10.1080/19491034.2017.1292191

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 60

  IyerA.KochA. J.HolaskaJ. M. (2017). Expression profiling of differentiating emerin-null myogenic progenitor identifies molecular pathways implicated in their impaired differentiation. Cells6, 38. 10.3390/cells6040038

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 61

  JiangW.XieN.XuC. (2022). Characterization of a prognostic model for lung squamous cell carcinoma based on eight stemness index-related genes. BMC Pulm. Med.22, 224. 10.1186/s12890-022-02011-0

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 62

  JiangH.KongN.LiuZ.WestS. C.ChanY. W. (2023). Human Endonuclease ANKLE1 localizes at the midbody and processes chromatin bridges to prevent DNA damage and cGAS‐STING activation. Adv. Sci.10, 2204388. 10.1002/advs.202204388

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 63

  KangS.XuH.DuanX.LiuJ. J.HeZ.YuF.et al (2000). PCD1, a novel gene containing PDZ and LIM domains, is overexpressed in several human cancers. Cancer Res.60, 5296–5302.

  • Pubmed Abstract
  • Google Scholar

• 64

  KangJ.LiN.WangF.WeiY.ZengY.LuoQ.et al (2022). Exploration of reduced mitochondrial content–associated gene signature and immunocyte infiltration in Colon adenocarcinoma by an integrated bioinformatic analysis. Front. Genet.13, 832331. 10.3389/fgene.2022.832331

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 65

  KimH.-J.HwangS.-H.HanM.-E.BaekS.SimH.-E.YoonS.et al (2012). LAP2 is widely overexpressed in diverse digestive tract cancers and regulates motility of cancer cells. PLoS ONE7, e39482. 10.1371/journal.pone.0039482

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 66

  KondéE.BourgeoisB.Tellier-LebegueC.WuW.PérezJ.CaputoS.et al (2010). Structural analysis of the Smad2−MAN1 interaction that regulates transforming growth Factor-β signaling at the inner nuclear membrane. Biochemistry49, 8020–8032. 10.1021/bi101153w

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 67

  LaguriC.GilquinB.WolffN.Romi-LebrunR.CourchayK.CallebautI.et al (2001). Structural characterization of the LEM motif common to three human inner nuclear membrane proteins. Structure9, 503–511. 10.1016/S0969-2126(01)00611-6

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 68

  LammerdingJ.HsiaoJ.SchulzeP. C.KozlovS.StewartC. L.LeeR. T. (2005). Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells. J. Cell Biol.170, 781–791. 10.1083/jcb.200502148

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 69

  LaTulippeE.SatagopanJ.SmithA.ScherH.ScardinoP.ReuterV.et al (2002). Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease. Cancer Res.62, 4499–4506.

  • Pubmed Abstract
  • Google Scholar

• 70

  LawrensonK.KarS.McCueK.KuchenbaekerK.MichailidouK.TyrerJ.et al (2016). Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast–ovarian cancer susceptibility locus. Nat. Commun.7, 12675. 10.1038/ncomms12675

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 71

  LiL.ZhangP. (2024). Elevation of LEM domain containing 1 predicts PoorPrognosis of NSCLC patients and triggers malignant stemnessand invasion of NSCLC cells by stimulating PI3K/AKT pathway. CMM24, 366–378. 10.2174/1566524023666230324135330

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 72

  LiD.WangD.LiuH.JiangX. (2022a). LEM domain containing 1 (LEMD1) transcriptionally activated by SRY-related high-mobility-group box 4 (SOX4) accelerates the progression of colon cancer by upregulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Bioengineered13, 8087–8100. 10.1080/21655979.2022.2047556

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 73

  LiJ.MahajanA.TsaiM.-D. (2006). Ankyrin repeat: a unique motif mediating Protein−Protein interactions. Biochemistry45, 15168–15178. 10.1021/bi062188q

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 74

  LiY.LiJ.WangY.ZhangY.ChuJ.SunC.et al (2017). Roles of cancer/testis antigens (CTAs) in breast cancer. Cancer Lett.399, 64–73. 10.1016/j.canlet.2017.02.031

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 75

  LiQ.GeY.ChenX.WangL.XiaY.XuZ.et al (2019). LEM domain containing 1 promotes proliferation via activating the PI3K/Akt signaling pathway in gastric cancer. J Cell. Biochem.120, 15190–15201. 10.1002/jcb.28783

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 76

  LiJ.LiangL.YangY.LiX.MaY. (2021). N6-methyladenosine as a biological and clinical determinant in colorectal cancer: progression and future direction. Theranostics11, 2581–2593. 10.7150/thno.52366

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 77

  LiZ.WangJ.WuJ.LiN.JiangC. (2022b). Long noncoding RNA LEMD1‐AS1 increases LEMD1 expression and activates PI3K‐AKT pathway to promote metastasis in oral squamous cell carcinoma. BioMed Res. Int.2022, 3543948. 10.1155/2022/3543948

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 78

  LiX.JiangS.JiangT.SunX.GuanY.FanS.et al (2023). LEM Domain containing 1 acts as a novel oncogene and therapeutic target for triple-negative breast cancer. Cancers15, 2924. 10.3390/cancers15112924

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 79

  LiddaneA. G.HolaskaJ. M. (2021). “The role of emerin in cancer progression and metastasis,” Int. J. Mol. Sci.1128922. 10.3390/ijms222011289

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 80

  LiddaneA. G.McNamaraC. A.CampbellM. C.MercierI.HolaskaJ. M. (2021). Defects in emerin–nucleoskeleton binding disrupt nuclear structure and promote breast cancer cell motility and metastasis. Mol. Cancer Res.19, 1196–1207. 10.1158/1541-7786.MCR-20-0413

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 81

  LinF.BlakeD. L.CallebautI.SkerjancI. S.HolmerL.McBurneyM. W.et al (2000). MAN1, an inner nuclear membrane protein that shares the LEM domain with lamina-associated polypeptide 2 and emerin. J. Biol. Chem.275, 4840–4847. 10.1074/jbc.275.7.4840

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 82

  LinF.MorrisonJ. M.WuW.WormanH. J. (2005). MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and Smad3 and antagonizes transforming growth factor-beta signaling. Hum. Mol. Genet.14, 437–445. 10.1093/hmg/ddi040

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 83

  LinC.-M.FangC.-L.HseuY.-C.ChenC.-L.WangJ.-W.HsuS.-L.et al (2013). Clinical and prognostic implications of transcription factor SOX4 in patients with Colon cancer. PLoS ONE8, e67128. 10.1371/journal.pone.0067128

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 84

  LinS.-T.ZhangL.LinX.ZhangL. C.GarciaV. E.TsaiC.-W.et al (2014). Nuclear envelope protein MAN1 regulates clock through BMAL1. eLife3, e02981. 10.7554/eLife.02981

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 85

  LiuY.WalavalkarN. M.DozmorovM. G.RichS. S.CivelekM.GuertinM. J. (2017). Identification of breast cancer associated variants that modulate transcription factor binding. PLoS Genet.13, e1006761. 10.1371/journal.pgen.1006761

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 86

  LiuC.YuH.ShenX.QiaoJ.WuX.ChangJ.et al (2019). Prognostic significance and biological function of Lamina-associated polypeptide 2 in non-small-cell lung cancer. OTT12, 3817–3827. 10.2147/OTT.S179870

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 87

  LuoZ.HaoS.YuanJ.ZhuK.LiuS.ZhangJ.et al (2021). Long non-coding RNA LINC00958 promotes colorectal cancer progression by enhancing the expression of LEM domain containing 1 via microRNA miR-3064-5p. Bioengineered12, 8100–8115. 10.1080/21655979.2021.1985259

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 88

  MackenzieK. J.CarrollP.MartinC.-A.MurinaO.FluteauA.SimpsonD. J.et al (2017). cGAS surveillance of micronuclei links genome instability to innate immunity. Nature548, 461–465. 10.1038/nature23449

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 89

  ManilalS.NguyenT. M.SewryC. A.MorrisG. E. (1996). The Emery-Dreifuss muscular dystrophy protein, emerin, is a nuclear membrane protein. Hum. Mol. Genet.5, 801–808. 10.1093/hmg/5.6.801

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 90

  MarkiewiczE.DechatT.FoisnerR.QuinlanR. A.HutchisonC. J. (2002). Lamin A/C binding protein LAP2alpha is required for nuclear anchorage of retinoblastoma protein. Mol. Biol. Cell13, 4401–4413. 10.1091/mbc.e02-07-0450

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 91

  MarkiewiczE.LedranM.HutchisonC. J. (2005). Remodelling of the nuclear lamina and nucleoskeleton is required for skeletal muscle differentiation in vitro. J. Cell Sci.118, 409–420. 10.1242/jcs.01630

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 92

  MarkiewiczE.TilgnerK.BarkerN.van de WeteringM.CleversH.DorobekM.et al (2006). The inner nuclear membrane protein emerin regulates beta-catenin activity by restricting its accumulation in the nucleus. EMBO J.25, 3275–3285. 10.1038/sj.emboj.7601230

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 93

  Marrero-RodríguezD.Taniguchi-PoncianoK.Lopez-SlemanJ.Romero-MorelosP.Mendoza-RodríguezM.GarciaI.et al (2015). Thymopoietin beta and gamma isoforms as a potential diagnostic molecular marker for breast cancer: preliminary data. Pathol. Oncol. Res.21, 1045–1050. 10.1007/s12253-015-9907-x

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 94

  Martinez-RomeroJ.Bueno-FortesS.Martín-MerinoM.Ramirez De MolinaA.De Las RivasJ. (2018). Survival marker genes of colorectal cancer derived from consistent transcriptomic profiling. BMC Genomics19, 857. 10.1186/s12864-018-5193-9

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 95

  MasicaD. L.KarchinR. (2011). Correlation of somatic mutation and expression identifies genes important in human glioblastoma progression and survival. Cancer Res.71, 4550–4561. 10.1158/0008-5472.CAN-11-0180

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 96

  MatsuyamaH.SuzukiH. I.NishimoriH.NoguchiM.YaoT.KomatsuN.et al (2011). miR-135b mediates NPM-ALK–driven oncogenicity and renders IL-17–producing immunophenotype to anaplastic large cell lymphoma. Blood118, 6881–6892. 10.1182/blood-2011-05-354654

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 97

  MirallesF.PosernG.ZaromytidouA.-I.TreismanR. (2003). Actin dynamics control SRF activity by regulation of its coactivator MAL. Cell113, 329–342. 10.1016/S0092-8674(03)00278-2

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 98

  Miranda-GonçalvesV.LoboJ.Guimarães-TeixeiraC.Barros-SilvaD.GuimarãesR.CantanteM.et al (2021). The component of the m6A writer complex VIRMA is implicated in aggressive tumor phenotype, DNA damage response and cisplatin resistance in germ cell tumors. J. Exp. Clin. Cancer Res.40, 268. 10.1186/s13046-021-02072-9

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 99

  MooneyS. M.RajagopalanK.RangarajanG.KulkarniP. (2016). Cancer/testis antigens and obligate participation in multiple hallmarks of cancer: an update. Asian J. Androl.18, 711–712. 10.4103/1008-682X.174858

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 100

  MuchirA.MedioniJ.LalucM.MassartC.ArimuraT.KooiAJVDet al (2004). Nuclear envelope alterations in fibroblasts from patients with muscular dystrophy, cardiomyopathy, and partial lipodystrophy carrying lamin A/C gene mutations. Muscle Nerve30, 444–450. 10.1002/mus.20122

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 101

  MuchirA.PavlidisP.BonneG.HayashiY. K.WormanH. J. (2007). Activation of MAPK in hearts of EMD null mice: similarities between mouse models of X-linked and autosomal dominant Emery–Dreifuss muscular dystrophy. Hum. Mol. Genet.16, 1884–1895. 10.1093/hmg/ddm137

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 102

  MuchirA.ShanJ.BonneG.LehnartS. E.WormanH. J. (2008). Inhibition of extracellular signal-regulated kinase signaling to prevent cardiomyopathy caused by mutation in the gene encoding A-type lamins. Hum. Mol. Genet.18, 241–247. 10.1093/hmg/ddn343

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 103

  MuchirA.WuW.WormanH. J. (2009). Reduced expression of A-type lamins and emerin activates extracellular signal-regulated kinase in cultured cells. Biochimica Biophysica Acta (BBA) - Mol. Basis Dis.1792, 75–81. 10.1016/j.bbadis.2008.10.012

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 104

  MüllerH.BrackenA. P.VernellR.MoroniM. C.ChristiansF.GrassilliE.et al (2001). E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosis. Genes Dev.15, 267–285. 10.1101/gad.864201

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 105

  MummS.WenkertD.ZhangX.McAlisterW. H.MierR. J.WhyteM. P. (2007). Deactivating germline mutations in LEMD3 cause osteopoikilosis and Buschke-Ollendorff syndrome, but not sporadic melorheostosis. J. Bone Min. Res.22, 243–250. 10.1359/jbmr.061102

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 106

  NaetarN.KorbeiB.KozlovS.KerenyiM. A.DornerD.KralR.et al (2008). Loss of nucleoplasmic LAP2alpha-lamin A complexes causes erythroid and epidermal progenitor hyperproliferation. Nat. Cell Biol.10, 1341–1348. 10.1038/ncb1793

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 107

  NaganoA.KogaR.OgawaM.KuranoY.KawadaJ.OkadaR.et al (1996). Emerin deficiency at the nuclear membrane in patients with Emery-Dreifuss muscular dystrophy. Nat. Genet.12, 254–259. 10.1038/ng0396-254

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 108

  NarayanankuttyA. (2019). PI3K/Akt/mTOR pathway as a therapeutic target for colorectal cancer: a review of preclinical and clinical evidence. Curr. Drug Targets20, 1217–1226. 10.2174/1389450120666190618123846

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 109

  NiliE.CojocaruG. S.KalmaY.GinsbergD.CopelandN. G.GilbertD. J.et al (2001). Nuclear membrane protein LAP2beta mediates transcriptional repression alone and together with its binding partner GCL (germ-cell-less). J. Cell Sci.114, 3297–3307. 10.1242/jcs.114.18.3297

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 110

  OsadaS.-I.OhmoriS.TairaM. (2003). XMAN1, an inner nuclear membrane protein, antagonizes BMP signaling by interacting with Smad1 in Xenopus embryos. Development130, 1783–1794. 10.1242/dev.00401

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 111

  PaganelliF.PoliA.TruocchioS.MartelliA. M.PalumboC.LattanziG.et al (2025). At the nucleus of cancer: how the nuclear envelope controls tumor progression. MedComm6, e70073. 10.1002/mco2.70073

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 112

  PalI.MandalM. (2012). PI3K and Akt as molecular targets for cancer therapy: current clinical outcomes. Acta Pharmacol. Sin.33, 1441–1458. 10.1038/aps.2012.72

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 113

  PanD.Estévez-SalmerónL. D.StroscheinS. L.ZhuX.HeJ.ZhouS.et al (2005). The integral inner nuclear membrane protein MAN1 physically interacts with the R-Smad proteins to repress signaling by the transforming growth factor-β superfamily of cytokines. J. Biol. Chem.280, 15992–16001. 10.1074/jbc.M411234200

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 114

  PariseP.FinocchiaroG.MasciadriB.QuartoM.FrancoisS.MancusoF.et al (2006). Lap2α expression is controlled by E2F and deregulated in various human tumors. Cell Cycle5, 1331–1341. 10.4161/cc.5.12.2833

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 115

  PawłowskiR.RajakyläE. K.VartiainenM. K.TreismanR. (2010). An actin-regulated importin α/β-dependent extended bipartite NLS directs nuclear import of MRTF-A. EMBO J.29, 3448–3458. 10.1038/emboj.2010.216

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 116

  PomeroyS. L.TamayoP.GaasenbeekM.SturlaL. M.AngeloM.McLaughlinM. E.et al (2002). Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature415, 436–442. 10.1038/415436a

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 117

  PonnurangamS.StandingD.RangarajanP.SubramaniamD. (2013). Tandutinib inhibits the Akt/mTOR signaling pathway to inhibit colon cancer growth. Mol. Cancer Ther.12, 598–609. 10.1158/1535-7163.MCT-12-0907

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 118

  PopędaM.KowalskiK.WentaT.BeznoussenkoG. V.RychłowskiM.MironovA.et al (2024). Emerin mislocalization during chromatin bridge resolution can drive prostate cancer cell invasiveness in a collagen-rich microenvironment. Exp. Mol. Med.56, 2016–2032. 10.1038/s12276-024-01308-w

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 119

  PrzanowskiP.PrzanowskaR. K.GuertinM. J. (2023). ANKLE1 cleaves mitochondrial DNA and contributes to cancer risk by promoting apoptosis resistance and metabolic dysregulation. Commun. Biol.6, 231. 10.1038/s42003-023-04611-w

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 120

  RaabM.GentiliM.De BellyH.ThiamH.-R.VargasP.JimenezA. J.et al (2016). ESCRT III repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death. Science352, 359–362. 10.1126/science.aad7611

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 121

  Reis-SobreiroM.ChenJ.-F.NovitskayaT.YouS.MorleyS.SteadmanK.et al (2018). Emerin deregulation links nuclear shape instability to metastatic potential. Cancer Res.78, 6086–6097. 10.1158/0008-5472.CAN-18-0608

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 122

  RoseM.BurgessJ. T.CheongC. M.AdamsM. N.ShahrouziP.O’ByrneK. J.et al (2024). The expression and role of the Lem-D proteins Ankle2, Emerin, Lemd2, and TMPO in triple-negative breast cancer cell growth. Front. Oncol.14, 1222698. 10.3389/fonc.2024.1222698

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 123

  RosnerA.MiyoshiK.Landesman-BollagE.XuX.SeldinD. C.MoserA. R.et al (2002). Pathway pathology. Am. J. Pathology161, 1087–1097. 10.1016/S0002-9440(10)64269-1

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 124

  RowatA. C.LammerdingJ.IpsenJ. H. (2006). Mechanical properties of the cell nucleus and the effect of emerin deficiency. Biophysical J.91, 4649–4664. 10.1529/biophysj.106.086454

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 125

  SalmaninejadA.ZamaniM. R.PourvahediM.GolchehreZ.Hosseini BereshnehA.RezaeiN. (2016). Cancer/Testis antigens: expression, regulation, tumor invasion, and use in immunotherapy of cancers. Immunol. Invest45, 619–640. 10.1080/08820139.2016.1197241

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 126

  SasahiraT.KuriharaM.NakashimaC.KiritaT.KuniyasuH. (2016). LEM domain containing 1 promotes oral squamous cell carcinoma invasion and endothelial transmigration. Br. J. Cancer115, 52–58. 10.1038/bjc.2016.167

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 127

  SasahiraT.Kurihara-ShimomuraM.NishiguchiY.ShimomuraH.KiritaT. (2020). Sushi repeat containing protein X-linked 2 is a downstream signal of LEM domain containing 1 and acts as a tumor-promoting factor in oral squamous cell carcinoma. IJMS21, 3655. 10.3390/ijms21103655

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 128

  SasakiM.TsujiN.FuruyaM.KondohK.KamagataC.KobayashiD.et al (2003). PCD1, a novel gene containing PDZ and LIM domains, is overexpressed in human breast cancer and linked to lymph node metastasis. Anticancer Res.23, 2717–2721.

  • Pubmed Abstract
  • Google Scholar

• 129

  ShaoC.LuC.ChenL.KotyP. P.CobosE.GaoW. (2011). p53-dependent anticancer effects of leptomycin B on lung adenocarcinoma. Cancer Chemother. Pharmacol.67, 1369–1380. 10.1007/s00280-010-1434-6

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 130

  SomechR.Nili Gal-YamE.ShaklaiS.GellerO.AmariglioN.RechaviG.et al (2007). Enhanced expression of the nuclear envelope LAP2 transcriptional repressors in normal and malignant activated lymphocytes. Ann. Hematol.86, 393–401. 10.1007/s00277-007-0275-9

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 131

  SongC.PangY.-Y.LuS.-Y.LiB.LiD.-M.HeR.-Q.et al (2025). Molecular mechanisms of thymopoietin in papillary thyroid cancer: multiplatform gene expression data, gene knockout screening, and in-house immunohistochemistry. World J. Clin. Oncol.16, 107109. 10.5306/wjco.v16.i7.107109

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 132

  SprangerS.BaoR.GajewskiT. F. (2015). Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature523, 231–235. 10.1038/nature14404

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 133

  StephensA. D.BaniganE. J.MarkoJ. F. (2019). Chromatin’s physical properties shape the nucleus and its functions. Curr. Opin. Cell Biol.58, 76–84. 10.1016/j.ceb.2019.02.006

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 134

  StevensK. N.VachonC. M.LeeA. M.SlagerS.LesnickT.OlswoldC.et al (2011). Common breast cancer susceptibility loci are associated with triple-negative breast cancer. Cancer Res.71, 6240–6249. 10.1158/0008-5472.CAN-11-1266

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 135

  StewartD. J.ChangD. W.YeY.SpitzM.LuC.ShuX.et al (2014). Wnt signaling pathway pharmacogenetics in non-small cell lung cancer. Pharmacogenomics J.14, 509–522. 10.1038/tpj.2014.21

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 136

  SunD.-P.LiewP.-L.LinC.-C.HungS.-T.ChenT.-C.FangC.-L.et al (2019). Clinicopathologic and prognostic significance of Thymopoietin-α overexpression in gastric cancer. J. Cancer10, 5099–5107. 10.7150/jca.30738

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 137

  TakedaR.HirohashiY.ShenM.WangL.OgawaT.MuraiA.et al (2017). Identification and functional analysis of variants of a cancer/testis antigen LEMD1 in colorectal cancer stem-like cells. Biochem. Biophysical Res. Commun.485, 651–657. 10.1016/j.bbrc.2017.02.081

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 138

  Tanaka-OkamotoM.HoriK.IshizakiH.HosoiA.ItohY.WeiM.et al (2009). Increased susceptibility to spontaneous lung cancer in mice lacking LIM-domain only 7. Cancer Sci.100, 608–616. 10.1111/j.1349-7006.2009.01091.x

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 139

  TangQ.ZhaoX.LiH.LiaoJ.OuyangB.MaC.et al (2025). LEM4 interacts with β-catenin and promotes β-catenin-dependent transcription activity to confers ribociclib resistance in breast cancer cells. Sci. Rep.15, 44435. 10.1038/s41598-025-28139-7

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 140

  TianJ.YingP.KeJ.ZhuY.YangY.GongY.et al (2020). ANKLE1 N6 -Methyladenosine-related variant is associated with colorectal cancer risk by maintaining the genomic stability. Int. J. Cancer146, 3281–3293. 10.1002/ijc.32677

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 141

  TilgnerK.WojciechowiczK.JahodaC.HutchisonC.MarkiewiczE. (2009). Dynamic complexes of A-type lamins and emerin influence adipogenic capacity of the cell via nucleocytoplasmic distribution of β-catenin. J. Cell Sci.122, 401–413. 10.1242/jcs.026179

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 142

  UlbertS.AntoninW.PlataniM.MattajI. W. (2006). The inner nuclear membrane protein Lem2 is critical for normal nuclear envelope morphology. FEBS Lett.580, 6435–6441. 10.1016/j.febslet.2006.10.060

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 143

  UmbreitN. T.ZhangC.-Z.LynchL. D.BlaineL. J.ChengA. M.TourdotR.et al (2020). Mechanisms generating cancer genome complexity from a single cell division error. Science368, eaba0712. 10.1126/science.aba0712

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 144

  Van SteenselB.BelmontA. S. (2017). Lamina-Associated domains: links with chromosome Architecture, Heterochromatin, and gene repression. Cell169, 780–791. 10.1016/j.cell.2017.04.022

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 145

  VargasJ. D.HatchE. M.AndersonD. J.HetzerM. W. (2012). Transient nuclear envelope rupturing during interphase in human cancer cells. Nucleus3, 88–100. 10.4161/nucl.18954

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 146

  VernellR.HelinK.MüllerH. (2003). Identification of target genes of the p16INK4A-pRB-E2F pathway. J. Biol. Chem.278, 46124–46137. 10.1074/jbc.M304930200

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 147

  VietriM.SchultzS. W.BellangerA.JonesC. M.PetersenL. I.RaiborgC.et al (2020). Unrestrained ESCRT-III drives micronuclear catastrophe and chromosome fragmentation. Nat. Cell Biol.22, 856–867. 10.1038/s41556-020-0537-5

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 148

  VigourouxC.AuclairM.DubosclardE.PoucheletM.CapeauJ.CourvalinJ.-C.et al (2001). Nuclear envelope disorganization in fibroblasts from lipodystrophic patients with heterozygous R482Q/W mutations in the lamin A/C gene. J. Cell Sci.114, 4459–4468. 10.1242/jcs.114.24.4459

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 149

  von AppenA.LaJoieD.JohnsonI. E.TrnkaM. J.PickS. M.BurlingameA. L.et al (2020). LEM2 phase separation promotes ESCRT-mediated nuclear envelope reformation. Nature582 (582), 115–118. 10.1038/s41586-020-2232-x

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 150

  VuralA.FadilliogluE.KelesogluF.MaD.LanierS. M. (2018). Role of G-proteins and phosphorylation in the distribution of AGS3 to cell puncta. J. Cell Sci.131, jcs216507. 10.1242/jcs.216507

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 151

  WangB.KouH.WangY.ZhangQ.JiangD.WangJ.et al (2024). LAP2α orchestrates alternative lengthening of telomeres suppression through telomeric heterochromatin regulation with HDAC1: unveiling a potential therapeutic target. Cell Death Dis.15, 761. 10.1038/s41419-024-07116-4

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 152

  WardM. C.Van Der WattP. J.TzonevaG.LeanerV. D. (2011). Deregulated LAP2α expression in cervical cancer associates with aberrant E2F and p53 activities. IUBMB Life63, 1018–1026. 10.1002/iub.528

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 153

  WatabeS.KobayashiS.HatoriM.NishijimaY.InoueN.IkotaH.et al (2021). Role of Lamin A and emerin in maintaining nuclear morphology in different subtypes of ovarian epithelial cancer. Oncol. Lett.23, 9. 10.3892/ol.2021.13127

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 154

  WilsonK. L.BerkJ. M. (2010). The nuclear envelope at a glance. J. Cell Sci.123, 1973–1978. 10.1242/jcs.019042

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 155

  WozniakM. A.BakerB. M.ChenC. S.WilsonK. L. (2013). The emerin-binding transcription factor Lmo7 is regulated by association with p130Cas at focal adhesions. PeerJ1, e134. 10.7717/peerj.134

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 156

  XuM.LinB.ZhengD.WenJ.HuW.LiC.et al (2021). LEM domain containing 1 promotes thyroid cancer cell proliferation and migration by activating the Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition. Oncol. Lett.21, 442. 10.3892/ol.2021.12703

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 157

  YadegariM.WhyteM. P.MummS.PhelpsR. G.ShanskeA.TottyW. G.et al (2010). Buschke-Ollendorff syndrome: absence of LEMD3 mutation in an affected family. Arch. Dermatol146, 63–68. 10.1001/archdermatol.2009.320

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 158

  YamC.GuY.OliferenkoS. (2013). Partitioning and remodeling of the Schizosaccharomyces japonicus Mitotic Nucleus require chromosome tethers. Curr. Biol.23, 2303–2310. 10.1016/j.cub.2013.09.057

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 159

  YangP.HuoZ.LiaoH.ZhouQ. (2015). Cancer/testis antigens trigger epithelial-mesenchymal transition and genesis of cancer stem-like cells. Curr. Pharm. Des.21, 1292–1300. 10.2174/1381612821666141211154707

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 160

  YangX.ZhouS.LiC.HuangL.ChenC.TangX.et al (2022). Downregulation of LEMD1-AS1 and its influences on the diagnosis, prognosis, and immune infiltrates of epithelial ovarian cancer. Dis. Markers2022, 6408879. 10.1155/2022/6408879

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 161

  YokotaN.MainprizeT. G.TaylorM. D.KohataT.LoretoM.UedaS.et al (2004). Identification of differentially expressed and developmentally regulated genes in medulloblastoma using suppression subtraction hybridization. Oncogene23, 3444–3453. 10.1038/sj.onc.1207475

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 162

  YonesakaK.KurosakiT.TanizakiJ.KawakamiH.TanakaK.MaenishiO.et al (2025). Chromosomal instability is associated with cGAS–STING activation in EGFR-TKI refractory non-small-cell lung cancer. Cells14, 447. 10.3390/cells14060447

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 163

  YukiD.LinY.-M.FujiiY.NakamuraY.FurukawaY. (2004). Isolation of LEM domain-containing 1, a novel testis-specific gene expressed in colorectal cancers. Oncol. Rep.12 (2), 275–280. 10.3892/or.12.2.275

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 164

  ZhangH.XuC.JiangF.FengJ. (2022). A three-genes signature predicting colorectal cancer relapse reveals LEMD1 promoting CRC cells migration by RhoA/ROCK1 signaling pathway. Front. Oncol.12, 823696. 10.3389/fonc.2022.823696

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 165

  ZhangY.CastoriM.FerrantiG.ParadisiM.WordsworthB. P. (2009). Novel and recurrent germline LEMD3 mutations causing Buschke-Ollendorff syndrome and osteopoikilosis but not isolated melorheostosis. Clin. Genet.75, 556–561. 10.1111/j.1399-0004.2009.01177.x

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 166

  ZhangB.Beeghly-FadielA.LongJ.ZhengW. (2011). Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence. Lancet Oncol.12, 477–488. 10.1016/S1470-2045(11)70076-6

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 167

  ZhangL.WangG.ChenS.DingJ.JuS.CaoH.et al (2016). Depletion of thymopoietin inhibits proliferation and induces cell cycle arrest/apoptosis in glioblastoma cells. World J. Surg. Onc14, 267. 10.1186/s12957-016-1018-y

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 168

  ZhangL.TengP.-C.CavassaniK. A.WangJ.GrassoC.WatsonJ.et al (2025). Emerin dysregulation drives the very-small-nuclear phenotype and lineage plasticity that associate with a clinically aggressive subtype of prostate cancer. Clin. Cancer Res.31, 2034–2045. 10.1158/1078-0432.CCR-24-3660

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 169

  ZhouT.LuP. (2024). Exosomal microRNA-21-5p from gastric cancer cells promotes angiogenesis by targeting LEMD3 in human endothelial cells. Oncologie26, 983–992. 10.1515/oncologie-2024-0198

  • CrossRef
  • Google Scholar

• 170

  ZinkD.FischerA. H.NickersonJ. A. (2004). Nuclear structure in cancer cells. Nat. Rev. Cancer4, 677–687. 10.1038/nrc1430

  • Pubmed Abstract
  • CrossRef
  • Google Scholar