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

Journal of Cellular Physiology
Xiaolu DuanGuohua Zeng

Abstract

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.

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Citations

Jul 31, 2016·Journal of Experimental & Clinical Cancer Research : CR·Laura Rosanò, Anna Bagnato
Sep 14, 2016·Biochemical and Biophysical Research Communications·Xiaolu DuanGuohua Zeng
Dec 22, 2017·JCI Insight·Lindsay Am ReinRobert J Lefkowitz
Feb 24, 2018·International Journal of Cancer. Journal International Du Cancer·Shuai JiangYang Yang
May 6, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jieping HuTing Sun
Nov 9, 2018·Oncology Letters·Shutong FanWeiguo Feng
Jun 29, 2016·Oncology Reports·Ye-Gong XieXu-Chen Cao
Jul 15, 2017·Cancer Metastasis Reviews·P GreseleM Sebastiano
Mar 7, 2019·Frontiers in Pharmacology·Anna Bagnato, Laura Rosanò
Oct 1, 2021·Pathology Oncology Research : POR·Muhammad Ihtisham UmarXianju Huang

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