Vps4A mediates the localization and exosome release of β-catenin to inhibit epithelial-mesenchymal transition in hepatocellular carcinoma

被引：49

作者：

Han, Qingfang ^{[1
,2
]}

Lv, Lihong ^{[3
]}

Wei, Jinxing ^{[2
]}

Lei, Xin ^{[4
]}

Lin, Haoming ^{[2
]}

Li, Guolin ^{[2
]}

Cao, Jun ^{[2
]}

Xie, Jiyan ^{[2
]}

Yang, Weibang ^{[2
]}

Wu, Shaobin ^{[2
]}

You, Jia ^{[5
]}

Lu, Jing ^{[5
]}

Liu, Peiqing ^{[5
]}

Min, Jun ^{[2
]}

机构：

[1] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510120, Guangdong, Peoples R China

[2] Sun Yat Sen Mem Hosp, Dept Hepatobiliary Surg, Guangzhou 510120, Guangdong, Peoples R China

[3] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Clin Trial Inst Pharmaceut, Guangzhou 510120, Guangdong, Peoples R China

[4] Sun Yat Sen Univ, Dept Thyroid & Breast Surg, Affiliated Hosp 1, Guangzhou 510080, Guangdong, Peoples R China

[5] Sun Yat Sen Univ, Sch Pharmaceut Sci, Lab Pharmacol & Toxicol, Guangzhou 510006, Guangdong, Peoples R China

来源：

CANCER LETTERS | 2019年 / 457卷

基金：

中国国家自然科学基金;

关键词：

ESCRT; Metastasis; Extracellular vesicles; MVS; Human hepatoma; ESCRT-III; EXTRACELLULAR VESICLES; MEMBRANE; MECHANISMS; PROTEIN;

D O I：

10.1016/j.canlet.2019.04.035

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We previously reported that Vps4A acted as a tumor suppressor by influencing the microRNA profiles of exosomes and their parental cells in hepatocellular carcinoma (HCC). However, the underlying mechanism and if Vps4A contributes to sorting proteins into exosomes are not well known. Here, we performed mass spectrometry analysis of the immunoprecipitated Vps4A complex and confirmed that Vps4A was associated with beta-catenin and CHMP4B. Through this interaction, Vps4A promoted the plasma membrane (PM) localization and exosome release of beta-catenin. Silencing Vps4A or CHMP4B decreased the PM localization and exosome sorting of beta-catenin. Vps4A overexpression decreased beta-catenin signaling pathway and inhibited epithelial-mesenchymal transition (EMT) and motility of HCC cells. And, silencing Vps4A or CHMP4B promoted EMT in HCC. Furthermore, the expression of Vps4A was significantly related to that of several EMT markers in HCC tissues and the level of exosomal beta-catenin in patients with metastatic HCC was significantly lower compared to that of control patients. In conclusion, through the interaction with CHMP4B and beta-catenin, Vps4A regulates the PM localization and exosome sorting of beta-catenin, consequently decreases beta-catenin signaling, and thereby inhibits EMT and metastasis in HCC.

引用

页码：47 / 59

页数：13

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