Mitochondrial unfolded protein response-dependent β-catenin signaling promotes neuroendocrine prostate cancer.

ABSTRACT: The mitochondrial unfolded protein response (UPR^mt) maintains mitochondrial quality control and proteostasis under stress conditions. However, the role of UPR^mt in aggressive and resistant prostate cancer is not clearly defined. We show that castration-resistant neuroendocrine prostate cancer (CRPC-NE) harbored highly dysfunctional oxidative phosphorylation (OXPHOS) Complexes. However, biochemical and protein analyses of CRPC-NE tumors showed upregulation of nuclear-encoded OXPHOS proteins and UPR^mt in this lethal subset of prostate cancer suggestive of compensatory upregulation of stress signaling. Genetic deletion and pharmacological inhibition of the main chaperone of UPR^mt heat shock protein 60 (HSP60) reduced neuroendocrine prostate cancer (

SUBMITTER: Woytash JA 

PROVIDER: S-EPMC12314736 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature