OPRK1 drives SLC9A3R1 progression to neuroendocrine prostate cancer.

ABSTRACT: Neuroendocrine differentiation (NED) plays a critical role in endocrine therapy resistance and dismal outcomes among prostate cancer (PCa) patients. The emergence of treatment-induced neuroendocrine prostate cancers (t-NEPCs) with the utilization of second-generation androgen receptor (AR) pathway inhibitors (ARPIs) poses a significant challenge, as the molecular underpinnings remain elusive. Here, our investigation unveils a close correlation between heightened levels of opioid receptor membrane protein OPRK1 and treatment-induced NED (t-NED), alongside an adverse prognosis in PCa cohorts. Our findings illuminate that AR represses OPRK1 transcription by binding to its promoter, a regulation amenable to reversal via ARPI administration. Further exploration reveals that OPRK1 stimulation tr

SUBMITTER: Liang L 

PROVIDER: S-EPMC12828004 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature