ORIGINAL RESEARCH article
Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1620122
EPHA2 Promotes Triple-Negative Breast Cancer Progression by Suppressing Pyroptosis via the AKT/PI3K/mTOR Pathway
Provisionally accepted
- 1Ningxia University, Yinchuan, China
- 2General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Region, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Breast cancer (BRCA) is the most prevalent cancer in women, with triple-negative breast cancer (TNBC) accounting for 15-20% of cases. TNBC is associated with higher rates of metastasis, recurrence, and poorer prognosis, underscoring the urgent need for new diagnostic and therapeutic strategies.: In this study, multiple public online platform, including UCSC Genome, UALCAN, Kaplan Meier plotter, DepMap and Single Cell Portal were used to detect the expression of EPHA2 in TNBC. Cell Counting Kit-8 (CCK-8) and transwell assays were conducted to assess proliferation and invasion. KOBAS bioinformatics, transmission electron microscopy (TEM), ELISA, western blot and quantitative realtime PCR experiments were employed to detect the association and effects of EPHA2 on pyroptosis in BRCA.Results: EPHA2 was highly expressed in TNBC, and showed a negative correlation with survival. Single-cell analysis indicated that EPHA2 was mainly expressed in stromal and epithelial cells, particularly within TNBC compartments. Furthermore, we found that EPHA2 knockdown inhibited cell proliferation and invasion, and induced pyroptosis, as evidenced by increased level of pyroptosis-related protein and characteristic morphological changes. Moreover, a relationship between EPHA2, pyroptosis, and the AKT/PI3K pathway was established and confirmed. Additionally, we observed a decreased expression of ferroptosis-associated marker named SLC7A11, suggesting that this transporter may mediate the effects of AKT inhibition on pyroptosis.In summary, our findings illuminated the dual roles of EPHA2 in TNBC, influencing both tumor progression and cell death pathways. We hypothesize that SLC7A11 serves as a key regulator of pyroptosis in the context of EPHA2 and AKT/PI3K signaling.These insights underscore the potential of targeting these pathways in developing therapeutic strategies for BRCA treatment. Further investigations into the mechanisms underlying SLC7A11's roles could enhance our understanding of its therapeutic implications.
Keywords: EphA2, pyroptosis, SLC7A11, Akt/PI3K, Triple-negative breast cancer
Received: 29 Apr 2025; Accepted: 30 Jul 2025.
Copyright: © 2025 Huang, Li, Han, Liu and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qilun Liu, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Region, China
Li-gang Wu, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Region, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.