DAB2IP loss confers the resistance of prostate cancer to androgen deprivation therapy through activating STAT3 and inhibiting apoptosis.

ABSTRACT: Loss of DAB2IP, a novel tumor suppressor gene, is associated with the high risk of aggressive prostate cancer (PCa). Previously, we reported that DAB2IP modulated androgen receptor activation in the development of castration-resistant PCa; however, its direct action on the failure of androgen deprivation therapy (ADT) remains largely unknown. In this study, we showed that DAB2IP knockdown could significantly enhance in vitro growth and colony formation of PCa cells following ADT as well as tumorigenicity in pre-castrated nude mice. In addition, DAB2IP loss stabilized mitochondrial transmembrane potential, prevented release of cytochrome c, Omi/HtrA2 and Smac from the mitochondria to the cytoplasm and inhibited intrinsic apoptosis induced by ADT. Mechanistically, DAB2IP could interact with

SUBMITTER: Zhou J 

PROVIDER: S-EPMC5399177 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature