FLOT1 promotes gastric cancer progression and metastasis through BCAR1/ERK signaling

FLOT1通过BCAR1 / ERK信号促进胃癌进展和转移

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作者:Ran Wang, Wei Huang, Kaimei Cai, Shihan Xiao, Wuming Zhang, Xianqin Hu, Jianping Guo, Linfeng Mao, Weijie Yuan, Yi Xu, Zihua Chen, Zhikang Chen, Chen Lai

Abstract

Flotillin-1 (FLOT1) is a member of the flotillin family and serves as a hallmark of lipid rafts involved in the process of signaling transduction and vesicular trafficking. Here, we find FLOT1 promotes gastric cancer cell progression and metastasis by interacting with BCAR1, through ERK signaling. FLOT1 regulates BCAR1 phosphorylation and translocation. Overexpression of FLOT1 increases, while knockdown of FLOT1 decreases gastric cancer cell proliferation, migration and invasion. BCAR1 knockdown could block FLOT1 induced gastric cancer cell proliferation, migration and invasion. Re-expression of wildtype rather than mutant BCAR1 (Y410F) could partially restore FLOT1 knockdown induced gastric cancer cell migration and invasion, while the restore could be inhibited by ERK inhibitor. Furthermore, FLOT1 and BCAR1 expression is closely related to gastric cancer patients' poor outcome. Thus, our findings confirm that BCAR1 mediates FLOT1 induced gastric cancer progression and metastasis through ERK signaling, which may provide a novel pathway for gastric cancer treatment.

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