Direct interaction between Rab5a and Rab4a enhanced epidermal growth factor-stimulated proliferation of gastric cancer cells  

作　　者：Guo-Jun Cao Di Wang Zhao-Pei Zeng Guo-Xiang Wang Chun-Jiu Hu Zhi-Fang Xing 

机构地区：[1]Department of Laboratory Medicine,Huashan Hospital North,Shanghai Medical College,Fudan University,Shanghai 201907,China [2]School of Life Sciences,Fudan University,Shanghai 200433,China [3]Department of Laboratory Medicine,Diniu(Shanghai)Health Technology Co.,Shanghai 201703,China [4]Department of Neurology,Institutes of Brain Science,State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science,Institute of Biological Science,Zhongshan Hospital,Fudan University,Shanghai 200032,China [5]Department of Gastroenterology,Ningbo First Hospital,Ningbo 315000,Zhejiang Province,China [6]Department of Laboratory Medicine,Huashan Hospital,Shanghai Medical College,Fudan University,Shanghai 200040,China

出　　处：《World Journal of Gastrointestinal Oncology》2021年第10期1492-1505,共14页世界胃肠肿瘤学杂志（英文版）（电子版）

基　　金：The Shanghai Health and Family Planning Commission,No.20154Y0141;Shanghai"Rising Stars of Medical Talent"Youth Development Program(Youth Medical Talents–Clinical Laboratory Practitioners Program);the Project of Huashan Hospital North,Fudan University,No.HSBY2019020.

摘　　要：BACKGROUND Gastric cancer(GC)is one of the leading causes of cancer-related death worldwide.Although targeted therapies such as antibodies against human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have been widely used in the treatment of metastatic cancer,the overall outcomes are poor.Therefore,elucidation of the mechanism underlying cancer progression is important to improve prognosis.Overexpression of the Rab5a gene has been confirmed to correlate with tumorigenesis of many cancers,but the mechanism underling,especially of GC,is still unclear.AIM To investigate the effects of Rab5a overexpression on the tumorigenesis of GC.METHODS First,the expression levels of Rab5a and Rab4a in primary tumorous tissues of GC patients diagnosed between 2015 and 2018 were analyzed.Then we constructed HGC-27 cell lines overexpressing green fluorescent protein-Rab5a or red fluorescent protein-Rab4a and investigated the interaction between Rab5a or Rab4a using Western blotting,co-immunoprecipitation,confocal microscopy,and colocalization analysis.Finally,epidermal growth factor-stimulated proliferation of these cell lines was analyzed using cell counting kit-8 cell viability assay.RESULTS Compared with normal gastric tissues,the expression levels of Rab5a and Rab4a increased progressively both in paracancerous tissues and in advanced cancerous tissues.Epidermal growth factor could promote the proliferation of HGC-27 cells,especially Rab5a-overexpressing HGC-27 cells.Notably,Rab5a and Rab4a cooverexpression promoted the proliferation of HGC-27 cells to the greatest extent.Further analysis identified a direct interaction between Rab5a and Rab4a in HGC-27 cells.CONCLUSION Co-overexpression of Rab5a and Rab4a in GC may promote the endosomal recycling of epidermal growth factor receptor,which in turn contributes to poor prognosis and tumor progression in GC patients.Inhibition of Rab5a or Rab4a expression might be a promising therapy for refractory GC.

关 键 词：Rab4a RAB5A Epidermal growth factor Cell proliferation Gastric cancer HGC-27 cell lines 

分 类 号：R735.2[医药卫生—肿瘤]