CAMK1D activates AMPK/PINK1/Parkin-dependent mitophagy to promote enzalutamide resistance in prostate cancer.

ABSTRACT: Although androgen receptor (AR)-targeted therapies, such as enzalutamide, initially improve outcomes of prostate cancer (PCa) patients, resistance inevitably develops, partly driven by prostate cancer stem-like cells (PCSCs). However, the molecular mechanisms linking the maintenance of PCSCs to enzalutamide resistance (ENZR) remain incompletely elucidated. Here, we implicate Ca²⁺/calmodulin-dependent protein kinase 1D (CAMK1D) in PCSC-mediated ENZR. CAMK1D was consistently upregulated in PCa with ENZR and contributed to ENZR by enhancing mitophagy in PCa cells both in vitro and in vivo. Mechanistically, CAMK1D promotes the expansion of PCSCs by enhancing mitophagy through activation of the AMP-activated protein kinase (AMPK)/PINK1 signaling pathway, thereby facilitating cellular adaptation

SUBMITTER: Sun F 

PROVIDER: S-EPMC12847848 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature