CST1 Interaction with RAB1B Modulates Tamoxifen resistance of Breast Cancer by Regulating Autophagy

Background: Breast cancer (BC) is a leading cause of cancer-related death in women worldwide, with approximately 70% of cases being estrogen receptor alpha-positive (ER+). Expression of the CST1 associated with metastasis of breast cancer and is linked with poor prognosis and poor survival. Methods: CST1 levels were measured using IHC, RT-qPCR, and Western Blot. Cell proliferation, invasion, and migration were evaluated using CCK-8 cell viability assays, colony formation assays, flow cytometry, Transwell assays, and TEM. Furthermore, the specific molecular mechanisms underlying CST1-mediated TAM resistance were elucidated through plasmid transfection, lentivirus infection, CO-IP, confocal microscopy, and Western Blot. Results: Elevated CST1 promotes the proliferation and migration of ER+ BC cells. Additionally, CST1 positively correlated with autophagy in ER+ BC cells, affecting TAM sensitivity. Further investigation revealed that CST1 interact with RAB1B, promoting autophagy and TAM resistance. Conclusion: These findings highlight CST1's regulatory role in modulating autophagy through its interaction with RAB1B, thereby increasing TAM resistance in ER+ BC.