TITLE

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

AUTHOR(S)
Duan, Xiaolu; Kong, Zhenzhen; Liu, Yang; Zeng, Zhiwen; Li, Shujue; Wu, Wenqi; Ji, Weidong; Yang, Bicheng; Zhao, Zhijian; Zeng, Guohua
PUB. DATE
October 2015
SOURCE
Journal of Cellular Physiology;Oct2015, Vol. 230 Issue 10, p2371
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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. J. Cell. Physiol. 230: 2371-2381, 2015. © 2015 Wiley Periodicals, Inc.
ACCESSION #
103383156

 

Related Articles

  • Serotonin promotes the proliferation of serumdeprived hepatocellular carcinoma cells via upregulation of FOXO3a. Chao Liang; Wei Chen; Xiao Zhi; Tao Ma; Xuefeng Xia; Hao Liu; Qi Zhang; Qida Hu; Yun Zhang; Xueli Bai; Tingbo Liang // Molecular Cancer;2013, Vol. 12 Issue 1, p1 

    Background: Peripheral serotonin is involved in tumorigenesis and induces a pro-proliferative effect in hepatocellular carcinoma (HCC) cells; however, the intracellular mechanisms by which serotonin exerts a mitogenic effect remain unclear. In this research, we examined whether FOXO3a, a...

  • LXRα-mediated downregulation of FOXM1 suppresses the proliferation of hepatocellular carcinoma cells. Hu, C; Liu, D; Zhang, Y; Lou, G; Huang, G; Chen, B; Shen, X; Gao, M; Gong, W; Zhou, P; Dai, S; Zeng, Y; He, F // Oncogene;5/29/2014, Vol. 33 Issue 22, p2888 

    Liver X receptors (LXRs), including LXRα and LXRβ isoforms, have important roles in the metabolic regulation of glucose, cholesterol and lipid. Moreover, activation of LXRs also represses the expression of cyclin D1 and cyclin B1, and thus suppresses the proliferation of multiple cancer...

  • MicroRNA-1269 promotes proliferation in human hepatocellular carcinoma via downregulation of FOXO1. Xue-Wei Yang; Guan-Zhu Shen; Liang-Qi Cao; Xiao-Feng Jiang; He-Ping Peng; Gang Shen; De Chen; Ping Xue // BMC Cancer;2014, Vol. 14 Issue 1, p1 

    Background Hepatocellular carcinoma (HCC) is one of the most common malignancies and a major cause of cancer-related mortality in the world. MicroRNAs (miRNAs) are small, noncoding RNAs that play essential roles in various stages during cancer progression. The aim of the current study was to...

  • Apigenin inhibits prostate cancer progression in TRAMP mice via targeting PI3K/Akt/FoxO pathway. Shukla, Sanjeev; Bhaskaran, Natarajan; Babcook, Melissa A.; Fu, Pingfu; MacLennan, Gregory T.; Gupta, Sanjay // Carcinogenesis;Feb2014, Vol. 35 Issue 2, p452 

    This study advances mechanistic understanding for the anticancer effects of a natural plant flavone apigenin that can inhibit prostate tumor growth and block metastasis by targeting PI3K/Akt/FoxO-mediated survival pathway.Forkhead box O (FoxO) transcription factors play an important role as...

  • A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer. Lunardi, Andrea; Ala, Ugo; Epping, Mirjam T; Salmena, Leonardo; Clohessy, John G; Webster, Kaitlyn A; Wang, Guocan; Mazzucchelli, Roberta; Bianconi, Maristella; Stack, Edward C; Lis, Rosina; Patnaik, Akash; Cantley, Lewis C; Bubley, Glenn; Cordon-Cardo, Carlos; Gerald, William L; Montironi, Rodolfo; Signoretti, Sabina; Loda, Massimo; Nardella, Caterina // Nature Genetics;Jul2013, Vol. 45 Issue 7, p747 

    Here we report an integrated analysis that leverages data from treatment of genetic mouse models of prostate cancer along with clinical data from patients to elucidate new mechanisms of castration resistance. We show that castration counteracts tumor progression in a Pten loss-driven mouse model...

  • EphA2 enhances the proliferation and invasion ability of LNCaP prostate cancer cells. PEIJIE CHEN; YAN HUANG; BO ZHANG; QIUQUAN WANG; PEIMING BAI // Oncology Letters;2014, Vol. 8 Issue 1, p41 

    numerous human cancers. However, to the best of our knowledge, the role that EphA2 plays in prostate cancer is not entirely clear. To investigate the roles of EphA2 in the development and progression of prostate cancer, the present study initially evaluated the roles of the EphA2 protein in...

  • Role of Androgen Receptor in Progression of LNCaP Prostate Cancer Cells from G1 to S Phase. Murthy, Shalini; Wu, Min; Bai, V. Uma; Hou, Zizheng; Menon, Mani; Barrack, Evelyn R.; Kim, Sahn-Ho; Reddy, G. Prem-Veer // PLoS ONE;Feb2013, Vol. 8 Issue 2, p1 

    Background: The androgen receptor (AR) plays a critical role in the proliferation of prostate cancer cells. However, its mechanism of action in proliferation remains unknown. An understanding of the mechanism of AR action in proliferation may lead to the development of effective strategies for...

  • The expression and functional role of FOX transcription factor FOXJ1 in prostate cancer. Qi An; Dezhong Liu; Lian Zou // International Journal of Clinical & Experimental Medicine;2017, Vol. 10 Issue 1, p285 

    As one common malignant tumor in male reproductive-urinary system, the incidence of prostate cancer is increasing rapidly. Recent study revealed the participation of FOX transcription factor family in tumor occurrence and progression. FOXJ1, one member of FOX family, plays an important role in...

  • Serum testosterone plays an important role in the metastatic ability of castration resistant prostate cancer. Sluis, Tim; Bijnsdorp, Irene; Jacobs, John; Meuleman, Eric; Rozendaal, Lawrence; Geldof, Albert; Moorselaar, R.; Vis, André // World Journal of Urology;Apr2013, Vol. 31 Issue 2, p261 

    Purpose: Prostate cells are dependent on androgens for growth and proliferation. Androgen deprivation therapy is the recommended treatment for advanced/metastatic prostate cancer. Under this therapy, prostate cancer will inevitably progress to castration resistant prostate cancer (CRPC). Despite...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics