Research Topic

TGF-β and BMP Signaling in Cancer

About this Research Topic

Transforming growth factor beta (TGF-β) family polypeptides are a group of ancient cytokines, which have evolved since the emergence of multicellular animals. The TGF-β family cytokines consist of over 30 members in mammals, including TGF-βs, bone morphogenetic proteins (BMPs), growth differentiation factors (GDFs), inhibins, activins, follistatin and anti-Müllerian hormone (AMH, also known as MIS). These secreted factors are grouped into two major subfamilies, i.e. the TGF-β and BMP subfamilies, based on their structural, biochemical and signaling properties. Intriguingly, TGF-β/BMPs share a similar membrane-to-nucleus signaling process, in which the ligand-bound membrane kinase receptors activate downstream transcription factors, the SMAD proteins. As produced or sensed by almost all cell types, TGF-β and BMPs are broadly engaged in fine-tuning embryonic development, organgenesis and tissue homeostasis. Deregulation of TGF-β signaling has been frequently found in human diseases including cancer. Among all the members of this family, TGF-β per se is the first to be appreciated playing a critical role in human cancer, and the most extensive studied and understood by now. TGF-β has been well documented to initiate a tumor suppressive pathway (the SMAD pathway) in most normal epithelial cell types, pre-malignant and even some malignant tumor cells, mainly by restraining cell proliferation and inducing apoptosis, in addition to suppressing the tumorigenic inflammation. However, once overcoming the growth inhibitory effects of TGF-β, cancer cells would take advantage of the oncogenic functions mediated by TGF-β, such as induction of epithelial-mesenchymal transition (EMT) and promotion of cancer cell survival, proliferation, migration, invasion and metastasis. In the process of tumor growth and metastasis, host cells in the tumor microenvironment (TME) often release TGF-β in large quantities, thereby not only promoting tumor survival but also profoundly altering their own behavioral patterns. Of relevance and noteworthy, TGF-β-mediated suppression of anti-tumor immunity has also been proven as an important barrier for cancer-related immune therapy. Finally, due to their far-ranging cellular roles including regulation of cell proliferation, death, motility, stemness and differentiation, the other TGF-β family cytokines are increasingly recognized to be intimately involved in both tumorigenesis and cancer progression in multiple organs.

This Research Topic aims to discuss the current understandings of the multifaceted roles of TGF-β family cytokines in tumorigenesis and cancer progression, including the molecular basis underlying both the tumor-suppressive and tumor-promoting effects of TGF-β and BMPs, in either cell-autonomous or cell-non-autonomous manners. Of the latter, it is increasingly realized that TGF-β is enriched in the tumor microenvironment, i.e. the stroma, and high expression level of TGF-β in cancer tissue or blood has been found to correlate with poor clinical outcome in patients. Therefore, understanding the role and mechanism of TGF-β in tumor microenvironment would be emphasized in this collection. Finally, how targeting TGF-β pathways is making headway in pre-clinical or clinical studies would also be discussed.

Specific themes:
1. How could cancer cells override the tumor-suppressive functions of TGF-β signaling?
2. What is the current molecular understanding underlying TGF-β-mediated cancer cell EMT, motility and dissemination?
3. How the functional switch of TGF-β in cancer cells is achieved?
4. What are the major functions of TGF-β in the tumor microenvironment?
5. What is the current status of TGF-β pathway-targeting therapies or combined therapies (e.g. that combining TGF-β pathway-targeting and antitumor immunotherapies) in pre-clinical and clinical studies, and any future perspectives?
6. How TGF-β signaling intersects with other cellular pathways during cancer progression and what are their major outcomes?


Keywords: TGF-β, BMP, Tumorigenesis, Cancer Progression, Tumor Microenvironment, Cancer Therapy


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Transforming growth factor beta (TGF-β) family polypeptides are a group of ancient cytokines, which have evolved since the emergence of multicellular animals. The TGF-β family cytokines consist of over 30 members in mammals, including TGF-βs, bone morphogenetic proteins (BMPs), growth differentiation factors (GDFs), inhibins, activins, follistatin and anti-Müllerian hormone (AMH, also known as MIS). These secreted factors are grouped into two major subfamilies, i.e. the TGF-β and BMP subfamilies, based on their structural, biochemical and signaling properties. Intriguingly, TGF-β/BMPs share a similar membrane-to-nucleus signaling process, in which the ligand-bound membrane kinase receptors activate downstream transcription factors, the SMAD proteins. As produced or sensed by almost all cell types, TGF-β and BMPs are broadly engaged in fine-tuning embryonic development, organgenesis and tissue homeostasis. Deregulation of TGF-β signaling has been frequently found in human diseases including cancer. Among all the members of this family, TGF-β per se is the first to be appreciated playing a critical role in human cancer, and the most extensive studied and understood by now. TGF-β has been well documented to initiate a tumor suppressive pathway (the SMAD pathway) in most normal epithelial cell types, pre-malignant and even some malignant tumor cells, mainly by restraining cell proliferation and inducing apoptosis, in addition to suppressing the tumorigenic inflammation. However, once overcoming the growth inhibitory effects of TGF-β, cancer cells would take advantage of the oncogenic functions mediated by TGF-β, such as induction of epithelial-mesenchymal transition (EMT) and promotion of cancer cell survival, proliferation, migration, invasion and metastasis. In the process of tumor growth and metastasis, host cells in the tumor microenvironment (TME) often release TGF-β in large quantities, thereby not only promoting tumor survival but also profoundly altering their own behavioral patterns. Of relevance and noteworthy, TGF-β-mediated suppression of anti-tumor immunity has also been proven as an important barrier for cancer-related immune therapy. Finally, due to their far-ranging cellular roles including regulation of cell proliferation, death, motility, stemness and differentiation, the other TGF-β family cytokines are increasingly recognized to be intimately involved in both tumorigenesis and cancer progression in multiple organs.

This Research Topic aims to discuss the current understandings of the multifaceted roles of TGF-β family cytokines in tumorigenesis and cancer progression, including the molecular basis underlying both the tumor-suppressive and tumor-promoting effects of TGF-β and BMPs, in either cell-autonomous or cell-non-autonomous manners. Of the latter, it is increasingly realized that TGF-β is enriched in the tumor microenvironment, i.e. the stroma, and high expression level of TGF-β in cancer tissue or blood has been found to correlate with poor clinical outcome in patients. Therefore, understanding the role and mechanism of TGF-β in tumor microenvironment would be emphasized in this collection. Finally, how targeting TGF-β pathways is making headway in pre-clinical or clinical studies would also be discussed.

Specific themes:
1. How could cancer cells override the tumor-suppressive functions of TGF-β signaling?
2. What is the current molecular understanding underlying TGF-β-mediated cancer cell EMT, motility and dissemination?
3. How the functional switch of TGF-β in cancer cells is achieved?
4. What are the major functions of TGF-β in the tumor microenvironment?
5. What is the current status of TGF-β pathway-targeting therapies or combined therapies (e.g. that combining TGF-β pathway-targeting and antitumor immunotherapies) in pre-clinical and clinical studies, and any future perspectives?
6. How TGF-β signaling intersects with other cellular pathways during cancer progression and what are their major outcomes?


Keywords: TGF-β, BMP, Tumorigenesis, Cancer Progression, Tumor Microenvironment, Cancer Therapy


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

15 December 2020 Abstract
31 March 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

15 December 2020 Abstract
31 March 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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