Caveolin-1 regulates hormone resistance through lipid synthesis, creating novel therapeutic opportunities for castration-resistant prostate cancer.

ABSTRACT: Caveolin-1 (Cav-1) is overexpressed in aggressive and metastatic prostate cancer (PCa) and induces PCa cell proliferation. Androgens mediate lipid synthesis through acetyl-CoA carboxylase-1 (ACC1) and fatty acid synthase (FASN). We investigated the Cav-1-mediated lipid synthesis in the development of castration resistance, and identified novel therapeutic opportunities. Using the PBCre+;Ptenloxp/loxp;PBCav-1+ mouse model we found that Cav-1 induction increased cancer incidence and growth, and ACC1-FASN expression in intact and castrated mice. We demonstrated that Cav-1 regulated ACC1 and FASN expression in an AR-independent way and increased palmitate synthesis using western blot analysis, qRT-PCR and mass spectrometry in vitro. By using FASN siRNA and C-75, we found that FASN inhibition w

SUBMITTER: Karantanos T 

PROVIDER: S-EPMC5216801 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature