GPX3 promotes cisplatin resistance in TNBC by manipulating ROS-TGFB1-ZEB2

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Triple-negative breast cancer (TNBC) presents a significant global health challenge due to limited effective therapies and high rates of acquired resistance.
• Platinum-based chemotherapy is a common treatment, but resistance mechanisms in TNBC require urgent investigation to identify new therapeutic targets.

Purpose of the Study:

• To investigate the role of GPX3 in platinum resistance in TNBC.
• To elucidate the signaling pathways involved in GPX3-mediated platinum resistance and epithelial-mesenchymal transition (EMT).

Main Methods:

• Compared GPX3 expression, cisplatin sensitivity, and ROS production in TNBC cell lines.
• Utilized RNA sequencing, bioinformatics, Western blotting, RNA interference, and mouse xenograft models.
• Analyzed GPX3, TGFB1, and ZEB2 correlations in clinical breast cancer samples and TCGA database.

Main Results:

• GPX3 upregulation promotes cisplatin resistance and is linked to increased invasiveness in TNBC cells.
• The GPX3-TGFB1-ZEB2 axis drives platinum resistance and metastasis via EMT.
• GPX3 depletion enhances platinum sensitivity, and its knockdown inhibits tumor growth in vivo.

Conclusions:

• GPX3 is a critical mediator of acquired platinum resistance and EMT in TNBC through the GPX3-TGFB1-ZEB2 pathway.
• GPX3 represents a promising biomarker and therapeutic target for improving diagnosis, treatment, and prognosis in high-risk TNBC patients.