β-Arrestin2 Contributes to Cell Viability and Proliferation via the Down-Regulation of FOXO1 in Castration-Resistant Prostate Cancer

Duan, Xiaolu; Kong, Zhenzhen; Liu, Yang; Zeng, Zhiwen; Li, Shujue; Wu, Wenqi; Ji, Weidong; Yang, Bicheng; Zhao, Zhijian; Zeng, Guohua
October 2015
Journal of Cellular Physiology;Oct2015, Vol. 230 Issue 10, p2371
Academic Journal
β-Arrestin2 has been identified to act as a corepressor of androgen receptor (AR) signaling by binding to AR and serving as a scaffold to affect the activity and expression of AR in androgen-dependent prostate cancer cells; however, little is known regarding its role in castration-resistant prostate cancer (CRPC) progression. Here, our data demonstrated that β-arrestin2 contributes to the cell viability and proliferation of CRPC via the downregulation of FOXO1 activity and expression. Mechanistically, in addition to its requirement for FOXO1 phosphorylation induced by IGF-1, β-arrestin2 could inhibit FOXO1 activity in an Akt-independent manner and delay FOXO1 dephosphorylation through the inhibition of PP2A phosphatase activity and the attenuation of the interaction between FOXO1 and PP2A. Furthermore, β-arrestin2 could downregulate FOXO1 expression via ubiquitylation and proteasomal degradation. Together, our results identified a novel role for β-arrestin2 in the modulation of the CRPC progress through FOXO1. Thus, the characterization of β-arrestin2 may represent an alternative therapeutic target for CRPC treatment. J. Cell. Physiol. 230: 2371-2381, 2015. © 2015 Wiley Periodicals, Inc.


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