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

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

更新时间：2022-06-24

- Depletion of VPS35 attenuates metastasis of hepatocellular carcinoma by restraining the Wnt/PCP signaling pathway
- Genes & Diseases Vol. 8, Issue 2, (2021)
- 作者机构：
  
  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,PR China,400016
  2. Department of Bioinformatics, School of Basic Medicine, Chongqing Medical University,Chongqing,PR China,400016
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2020.07.009
  CLC：
- Published：2021，
  
  Published Online：1 March 2021，
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Yi Liu, Haijun Deng, Li Liang, et al. Depletion of VPS35 attenuates metastasis of hepatocellular carcinoma by restraining the Wnt/PCP signaling pathway. [J]. Genes & Diseases 8(2).(2021)
DOI：

Yi Liu, Haijun Deng, Li Liang, et al. Depletion of VPS35 attenuates metastasis of hepatocellular carcinoma by restraining the Wnt/PCP signaling pathway. [J]. Genes & Diseases 8(2).(2021) DOI： 10.1016/j.gendis.2020.07.009.

摘要

Abstract

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.

关键词

Keywords

Epithelial–mesenchymal transitionHepatocellular carcinoma (HCC)MetastasisRetromer complexVPS35Wnt/PCP signaling pathway

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