Stat5 induces androgen receptor (<i>AR</i>) gene transcription in prostate cancer and offers a druggable pathway to target AR signaling.

ABSTRACT: Androgen receptor (AR) drives prostate cancer (PC) growth and progression, and targeting AR signaling is the mainstay of pharmacological therapies for PC. Resistance develops relatively fast as a result of refueled AR activity. A major gap in the field is the lack of understanding of targetable mechanisms that induce persistent AR expression in castrate-resistant PC (CRPC). This study uncovers an unexpected function of active Stat5 signaling, a known promoter of PC growth and clinical progression, as a potent inducer of AR gene transcription. Stat5 suppression inhibited AR gene transcription in preclinical PC models and reduced the levels of wild-type, mutated, and truncated AR proteins. Pharmacological Stat5 inhibition by a specific small-molecule Stat5 inhibitor down-regula

SUBMITTER: Maranto C 

PROVIDER: S-EPMC10901378 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature