G3BP1 promotes human breast cancer cell proliferation through coordinating with GSK-3β and stabilizing β-catenin  

作　　者：Cong-hui Zhang Hong Liu Wu-li Zhao Wen-xia Zhao Hui-min Zhou Rong-guang Shao 

机构地区：[1]Key Laboratory of Antibiotic Bioengineering,Ministry of Health,Laboratory of Oncology,Institute of Medicinal Biotechnology,Peking Union Medical College and Chinese Academy of Medical Sciences,Beijing 100050,China

出　　处：《Acta Pharmacologica Sinica》2021年第11期1900-1912,共13页中国药理学报（英文版）

基　　金：supported by the National Key Research and Development Program of China(2016YFA0201504);National Natural Science Foundation of China(No.81673471,81102464);the CAMS Initiative for Innovative Medicine(2016-I2M-2-002);the Drug Innovation Major Project of China(2018ZX09711001-007-002).

摘　　要：Ras-GTPase activating SH3 domain-binding protein 1(G3BP1)is a multifunctional binding protein involved in the development of a variety of human cancers.However,the role of G3BP1 in breast cancer progression remains largely unknown.In this study,we report that G3BP1 is upregulated and correlated with poor prognosis in breast cancer.Overexpression of G3BP1 promotes breast cancer cell proliferation by stimulatingβ-catenin signaling,which upregulates a number of proliferation-related genes.We further show that G3BP1 improves the stability ofβ-catenin by inhibiting its ubiquitin-proteasome degradation rather than affecting the transcription ofβ-catenin.Mechanistically,elevated G3BP1 interacts with and inactivates GSK-3βto suppressβ-catenin phosphorylation and degradation.Disturbing the G3BP1-GSK-3βinteraction accelerates the degradation ofβ-catenin,impairing the proliferative capacity of breast cancer cells.Our study demonstrates that the regulatory mechanism of the G3BP1/GSK-3β/β-catenin axis may be a potential therapeutic target for breast cancer.

关 键 词：G3BP1 Wnt/β-catenin signaling pathway GSK-3βphosphorylation protein stability breast cancer peptide antagonist 

分 类 号：R737.9[医药卫生—肿瘤]