Osteopontin Promotes Epithelial-mesenchymal Transition of Hepatocellular Carcinoma Through Regulating Vimentin

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Jan 30

PMID 26824421

Citations 42

Authors

Qiongzhu Dong

Xuchao Zhu

Chun Dai

Xiaofei Zhang

Xiaomei Gao

Jinwang Wei

Yuanyuan Sheng

Yan Zheng

Jian Yu

Lu Xie

Yi Qin

Peng Qiao

Chuang Zhou

Xinxin Yu

Huliang Jia

Ning Ren

Haijun Zhou

Qinghai Ye

Lunxiu Qin

Affiliations

Soon will be listed here.

Abstract

Our previous studies have found that osteopontin (OPN) is a promoter for hepatocellular carcinoma (HCC) progression. However, the molecular mechanism by which OPN enhances HCC metastasis remains elusive. Epithelial-mesenchymal transition (EMT) of cancer cells plays a pivotal role in promoting metastatic process. In this study, we demonstrated that OPN promotes HCC metastasis by inducing an EMT-like, more aggressive cellular phenotype in vitro and in vivo. Furthermore, OPN was identified to interact with vimentin by reciprocal OPN and vimentin immunoprecipitation as well as co-immunofluorescence examination. By using deletion mutants, we found that the residues between 246 and 406 in vimentin are required for binding to OPN. Importantly, OPN significantly increased vimentin stability through inhibition of its protein degradation. Knockdown of vimentin neutralized the EMT induced by OPN both in vitro and in vivo. Moreover, a significant correlation between OPN and vimentin levels was found in clinical HCC specimens and their combination had a worse prognosis with shorter overall survival (OS) and time to recurrence (TTR). In multivariate analysis, OPN and their combination were demonstrated to be independent prognostic indicators for OS and TTR of HCC patients. Collectively, this study indicates that OPN can induce EMT of HCC cells through increasing vimentin stability, which provides more in-depth understanding about the molecular mechanisms of OPN in promoting HCC metastasis and opens tantalizing therapeutic possibilities in HCC.

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