Depletion of VPS35 attenuates metastasis of hepatocellular carcinoma by restraining the Wnt/PCP signaling pathway

查看全文 作　　者：Yi [1]Liu;Haijun [1]Deng;Li [1]Liang;Guiji [1]Zhang;Jie [1]Xia;Keyue [2]Ding;Ni [1]Tang;Kai [1]Wang

机构地区：[1]Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education),Institute for Viral Hepatitis,Department of Infectious Diseases,The Second Affiliated Hospital,Chongqing Medical University,Chongqing,400016,PR China;[2]Department of Bioinformatics,School of Basic Medicine,Chongqing Medical University,Chongqing,400016,PR China

出　　处：《Genes & Diseases》索引2021年第8卷第2期,共9页

基　　金：This work was supported by National Natural Science Foundation of China(grant numbers 81872270 and 81572683 to NT),the Natural Science Foundation Project of Chongqing(cstc2019jcyj-msxmX0587 to KW),the Science and Technology Research Program of Chongqing Municipal Education Commission(Grant number KJQN201900429 to KW),the Major National S&T program(2017ZX10202203-004 to NT),Natural Science Foundation Project of CQ CSTC(cstc2018jcyjAX0254 to NT),and the Leading Talent Program of CQ CSTC(CSTCCXLJRC201719 to NT). 摘　　要：Vesicle Protein Sorting 35(VPS35)is a novel oncogene that promotes tumor growth through the PI3K/AKT signaling in hepatocellular carcinoma(HCC).However,the role of VPS35 in HCC metastasis and the underlying mechanisms remain largely unclear.In this study,we observed that overexpression of VPS35 enhanced hepatoma cell invasion and metastasis by inducing epithelialemesenchymal transition(EMT)-related gene expression.Conversely,knockout of VPS35 significantly inhibited hepatoma cell migration and invasion.Furthermore,depletion of VPS35 decreased the lung metastasis of HCC in nude mice.By transcriptome analysis,we determined that VPS35 promoted HCC metastasis by activating the Wnt/non-canonical planar cell polarity(PCP)pathway.Mechanistically,VPS35 activated the PCP pathway by regulating membrane sorting and trafficking of Frizzled-2(FZD2)and ROR1 in hepatoma cells.Collectively,our results indicate that VPS35 promotes HCC metastasis via enhancing the Wnt/PCP signaling,thus providing a potential prognostic marker and therapeutic target for HCC. 关键词：Epithelial emesenchymal transition Hepatocellular carcinoma(HCC) METASTASIS Retromer complex VPS35 Wnt/PCP signaling pathway

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Depletion of VPS35 attenuates metastasis of hepatocellular carcinoma by restraining the Wnt/PCP signaling pathway

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