TMEM45A enhances palbociclib resistance and cellular glycolysis by activating AKT/mTOR signaling pathway in HR+ breast cancer.

ABSTRACT: Palbociclib, a CDK4/6 inhibitor, plays a crucial role in the treatment of HR+ breast cancer. However, resistance to palbociclib is a significant concern that merits further investigation. Our investigation identifies TMEM45A as a potential driver of palbociclib resistance and its association with increased cellular glycolysis. We demonstrate that TMEM45A is highly expressed in palbociclib-resistant breast cancer (BRCA) cells, correlating with enhanced tumor progression. Silencing TMEM45A enhances sensitivity to palbociclib, promotes cell cycle arrest and apoptosis, and inhibits the proliferation of BRCA cells. Moreover, attenuation of TMEM45A expression reduces cancer aggressiveness by decreasing the expression of EMT and glycolysis-related proteins. Subsequent gene set enrichment analysis

SUBMITTER: Chen C 

PROVIDER: S-EPMC11799145 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature