Enzalutamide-Resistant STEAP4⁺ MyoCAF Secrete Phosphatidylcholine to Foster Progression by Activating Stemness in Hormone-Sensitive Prostate Cancer.

ABSTRACT: Despite the expanding clinical application of second-generation anti-androgens like enzalutamide (ENZ) in hormone-sensitive prostate cancer (HSPC), therapeutic resistance culminating in castration-resistant prostate cancer (CRPC) persists as an unresolved clinical crisis. Through comprehensive single-cell transcriptomic profiling of ENZ-naïve and ENZ-treated tumors, an expansion of ENZ-resistant myofibroblastic cancer-associated fibroblast (designated STEAP4⁺ myoCAF) is identified that correlates with adverse clinical outcomes. Strikingly, STEAP4⁺ myoCAF demonstrated intrinsic ENZ resistance through a mechanistically novel pathway involving transcription factor binding to IGHM enhancer 3 (TFE3)-mediated autophagy activation. Integrated lipidomic and functional analyse

SUBMITTER: Wang W 

PROVIDER: S-EPMC12667479 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature