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

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

  • J Exp Clin Cancer Res. 2018 Jun 28;37(1):128. doi: 10.1186/s13046-018-0787-2.
Xueran Chen 1 2,  Shangrong Zhang 1 2,  Zhen Wang 1 3,  Fengsong Wang 4,  Xinwang Cao 4,  Quan Wu 5,  Chenggang Zhao 1 3,  Huihui Ma 3 6,  Fang Ye 2,  Hongzhi Wang 1 2,  Zhiyou Fang 7 8
Affiliations

Affiliations

  • 1 Anhui Province Key Laboratory of Medical Physics and Technology, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, 230031, Anhui, China.
  • 2 Hefei Cancer Hospital, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, 230031, Anhui, China.
  • 3 University of Science and Technology of China, No. 96, Jin Zhai Road, Hefei, 230026, Anhui, China.
  • 4 School of Life Science, Anhui Medical University, No. 81, Mei Shan Road, Hefei, 230032, Anhui, China.
  • 5 Central Laboratory of Medical Research Center, Anhui Provincial Hospital, No. 17, Lu Jiang Road, Hefei, 230001, Anhui, China.
  • 6 Department of Radiation Oncology, First Affiliated Hospital, Anhui Medical University, No. 81, Mei Shan Road, Hefei, 230032, Anhui, China.
  • 7 Anhui Province Key Laboratory of Medical Physics and Technology, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, 230031, Anhui, China. z.fang@cmpt.ac.cn.
  • 8 Hefei Cancer Hospital, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, 230031, Anhui, China. z.fang@cmpt.ac.cn.
PMID: 29954442 DOI: 10.1186/s13046-018-0787-2
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.

Keywords

EMT; ERK/P38; HCC; RhoA/ROCK; Supervillin.

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