Yes‐associated protein, YAP, functions as a positive regulator of androgen receptor signaling in prostate cancer cells

Abstract

Androgen receptor (AR) plays a central role in prostate tumor biology. Here, we studied the impact of yes‐associated protein (YAP) oncogene, a nuclear effector of the hippo tumor suppressor network, on AR signaling. We first showed that native YAP formed protein complexes with endogenous AR, and the complex formation that mainly occurred in cell nuclei was enhanced by androgen, as revealed by immunoprecipitation (IP) and western blots. Our promoter reporter analysis demonstrated that enforced YAP expression increased the activation of AR‐dependent promoter reporter gene, and that the carboxyl‐terminal site of YAP, which consists of WW and coiled‐coiled domains, appeared to be responsible for AR transactivation. Chromatin‐IP experiment demonstrated that YAP interacted with the DNA regions where AR also binds, and that androgen enhanced the YAP and chromatin DNA complexes. We also provide evidence that YAP induction promoted an androgen‐dependent and ‐independent cell growth, and that YAP knockdown had the opposite effects. Our data indicate that YAP is a binding partner and physiologic positive regulator of AR and suggest that altered Hippo‐YAP signaling could play a critical role in prostate tumor progression in humans.