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

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World Journal of Gastrointestinal Oncology 2021年第10期13卷 1492-1505页

作者： Guo-Jun Cao Di Wang Zhao-Pei Zeng Guo-Xiang Wang Chun-Jiu Hu Zhi-Fang Xing Department of Laboratory Medicine Huashan Hospital NorthShanghai Medical CollegeFudan UniversityShanghai 201907China School of Life Sciences Fudan UniversityShanghai 200433China Department of Laboratory Medicine Diniu(Shanghai)Health Technology Co.Shanghai 201703China Department of Neurology Institutes of Brain ScienceState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitute of Biological ScienceZhongshan HospitalFudan UniversityShanghai 200032China Department of Gastroenterology Ningbo First HospitalNingbo 315000Zhejiang ProvinceChina Department of Laboratory Medicine Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200040China

BACKGROUND Gastric cancer(GC)is one of the leading causes of cancer-related death *** 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 ***,elucidation of the mechanism underlying cancer progression is important to improve *** of the Rab5a gene has been confirmed to correlate with tumorigenesis of many cancers,but the mechanism underling,especially of GC,is still *** To investigate the effects of Rab5a overexpression on the tumorigenesis of *** First,the expression levels of Rab5a and Rab4a in primary tumorous tissues of GC patients diagnosed between 2015 and 2018 were *** 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 ***,epidermal growth factor-stimulated proliferation of these cell lines was analyzed using cell counting kit-8 cell viability *** Compared with normal gastric tissues,the expression levels of Rab5a and Rab4a increased progressively both in paracancerous tissues and in advanced cancerous *** growth factor could promote the proliferation of hgc-27 cells,especially Rab5a-overexpressing hgc-27 ***,Rab5a and Rab4a cooverexpression promoted the proliferation of hgc-27 cells to the greatest *** analysis identified a direct interaction between Rab5a and Rab4a in hgc-27 *** 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 *** of Rab5a or Rab4a expression might be a promising therapy for refractory

关键词： Rab4a Rab5a Epidermal growth factor cell proliferation Gastric cancer hgc-27 cell lines

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