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

作者全名："Liu, Yi; Deng, Haijun; Liang, Li; Zhang, Guiji; Xia, Jie; Ding, Keyue; Tang, Ni; Wang, Kai"

作者地址："[Liu, Yi; Deng, Haijun; Liang, Li; Zhang, Guiji; Xia, Jie; Tang, Ni; Wang, Kai] Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Inst Viral Hepatitis, Minist Educ,Dept Infect Dis,Affiliated Hosp 2, Chongqing 400016, Peoples R China; [Ding, Keyue] Chongqing Med Univ, Sch Basic Med, Dept Bioinformat, Chongqing 400016, Peoples R China"

通信作者："Tang, N; Wang, K (corresponding author), Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Inst Viral Hepatitis, Minist Educ,Dept Infect Dis,Affiliated Hosp 2, Chongqing 400016, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000644364000014

JCR分区：Q1

影响因子：6.8

年份：2021

卷号：8

期号：2

开始页：232

结束页：240

文献类型：Article

关键词：Epithelial-mesenchymal transition; Hepatocellular carcinoma (HCC); Metastasis; Retromer complex; VPS35; Wnt/PCP signaling pathway

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 epithelial-mesenchymal 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. Copyright (C) 2020, Chongqing Medical University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81872270, 81572683]; Natural Science Foundation Project of ChongqingNatural Science Foundation of Chongqing [cstc2019jcyjmsxmX0587]; Science andTechnology Research Program of Chongqing Municipal Education Commission [KJQN201900429]; Major National ST program [2017ZX10202203-004]; Natural Science Foundation Project of CQ CSTCNatural Science Foundation Project of CQ CSTC [cstc2018jcyjAX0254]; Leading Talent Program of CQ CSTC [CSTCCXLJRC201719]"

基金资助正文："We would like to thank Dr. TongChuan He (University of Chicago, USA) for providing the pAdEasy plasmid system. 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 (cstc2019jcyjmsxmX0587 to KW) , the Science andTechnology 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) ."