A TBX2-driven signaling switch from androgen receptor to glucocorticoid receptor confers therapeutic resistance in prostate cancer.

ABSTRACT: Recent studies suggest that glucocorticoid receptor (GR) activation can cause enzalutamide resistance in advanced prostate cancer (PCa) via functional bypass of androgen receptor (AR) signaling. However, the specific molecular mechanism(s) driving this process remain unknown. We have previously reported that the transcription factor TBX2 is over-expressed in castrate-resistant prostate cancer (CRPC). In this study, using human PCa and CRPC cell line models, we demonstrate that TBX2 downregulates AR and upregulates GR through direct transcriptional regulation. TBX2 also activated the GR via TBX2-GR protein-protein interactions. Together, TBX2-driven repression of AR and activation of GR resulted in enzalutamide resistance. Our laboratory findings are supported by clinical samples, which sho

SUBMITTER: Dutta S 

PROVIDER: S-EPMC11932930 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature