RGS4 promotes the progression of gastric cancer through the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition  

作　　者：Peng-Yu Chen Pei-Yao Wang Bang Liu Yang-Pu Jia Zhao-Xiong Zhang Xin Liu Dao-Han Wang Yong-Jia Yan Wei-Hua Fu Feng Zhu 

机构地区：[1]Department of General Surgery,Tianjin Medical University General Hospital,Tianjin Medical University,Tianjin 300052,China [2]Department of General Surgery,Jincheng People’s Hospital,Jincheng 048000,Shanxi Province,China

出　　处：《World Journal of Gastroenterology》2025年第2期113-127,共15页世界胃肠病学杂志（英文）

基　　金：Supported by the Fundamental Research Program of Shanxi Province,No.202203021222418;Research Program of Shanxi Provincial Health Commission,No.2023061;Fundamental Research Cooperation Program of Beijing-Tianjin-Hebei Region of Natural Science Foundation of Tianjin,No.22JCZXJC00140;Tianjin Major Science and Technology Project,No.21ZXJBSY00110;Tianjin Health and Science and Technology Project,No.TJWJ2024ZK001.

摘　　要：BACKGROUND Regulator of G protein signaling(RGS)proteins participate in tumor formation and metastasis by acting on theα-subunit of heterotrimeric G proteins.The speci-fic effect of RGS,particularly RGS4,on the progression of gastric cancer(GC)is not yet clear.AIM To explore the role and underlying mechanisms of action of RGS4 in GC develop-ment.METHODS The prognostic significance of RGS4 in GC was analyzed using bioinformatics based public databases and verified by immunohistochemistry and quantitative polymerase chain reaction in 90 patients with GC.Function assays were employed to assess the carcinogenic impact of RGS4,and the mechanism of its possible influence was detected by western blot analysis.A nude mouse xenograft model was established to study the effects of RGS4 on GC growth in vitro.RESULTS RGS4 was highly expressed in GC tissues compared with matched adjacent normal tissues.Elevated RGS4 expression was correlated with increased tumor-node-metastasis stage,increased tumor grade as well as poorer overall survival in patients with GC.Cell experiments demonstrated that RGS4 knockdown suppressed GC cell proliferation,migration and invasion.Similarly,xenograft experiments confirmed that RGS4 silencing significantly inhibited tumor growth.Moreover,RGS4 knockdown resulted in reduced phosphorylation levels of focal adhesion kinase,phosphatidyl-inositol-3-kinase,and protein kinase B,decreased vimentin and N-cadherin,and elevated E-cadherin.CONCLUSION High RGS4 expression in GC indicates a worse prognosis and RGS4 is a prognostic marker.RGS4 influences tumor progression via the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition.

关 键 词：Gastric cancer Prognosis Regulator of G protein signaling 4 Focal adhesion kinase Epithelial-mesenchymal transition 

分 类 号：R735.7[医药卫生—肿瘤]