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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Research

Supervillin promotes epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma in hypoxia via activation of the RhoA/ROCK-ERK/p38 pathway

Authors: Xueran Chen, Shangrong Zhang, Zhen Wang, Fengsong Wang, Xinwang Cao, Quan Wu, Chenggang Zhao, Huihui Ma, Fang Ye, Hongzhi Wang, Zhiyou Fang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

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Abstract

Background

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and metastasis is the leading cause of death associated with HCC. Hypoxia triggers the epithelial-mesenchymal transition (EMT) of cancer cells, which enhances their malignant character and elevates metastatic risk. Supervillin associates tightly with the membrane and cytoskeleton, promoting cell motility, invasiveness, and cell survival. However, the roles of supervillin in HCC metastasis remain unclear.

Methods

Tissue microarray technology was used to immunohistochemically stain for supervillin antibody in 173 HCC tissue specimens and expression levels correlated with the clinicopathological variables. Tumor cell motility and invasiveness, as well as changes in the mRNA expression levels of genes associated with cancer cell EMT, were investigated. The relationship between supervillin and Rho GTPases was examined using Co-IP and GST pull-down.

Results

Hypoxia-induced upregulation of supervillin promoted cancer cell migration and invasion via the activation of the ERK/p38 pathway downstream of RhoA/ROCK signaling. Furthermore, supervillin regulated the expression of EMT genes during hypoxia and accelerated the metastasis of HCC in vivo.

Conclusions

Hypoxia-induced increase in supervillin expression is a significant and independent predictor of cancer metastasis, which leads to poor survival in HCC patients. Our results suggest that supervillin may be a candidate prognostic factor for HCC and a valuable target for therapy.
Appendix
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Metadata
Title
Supervillin promotes epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma in hypoxia via activation of the RhoA/ROCK-ERK/p38 pathway
Authors
Xueran Chen
Shangrong Zhang
Zhen Wang
Fengsong Wang
Xinwang Cao
Quan Wu
Chenggang Zhao
Huihui Ma
Fang Ye
Hongzhi Wang
Zhiyou Fang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-018-0787-2

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