Overexpression of RhoGDI, a novel predictor of distant metastasis, promotes cell proliferation and migration in hepatocellular carcinoma

Hui Wang; Bin Wang; Qing Liao; Hongying An; Weidong Li; Xuejun Jin; Shuzhong Cui; Liang Zhao

doi:10.1016/j.febslet.2013.12.016

Overexpression of RhoGDI, a novel predictor of distant metastasis, promotes cell proliferation and migration in hepatocellular carcinoma

FEBS Lett. 2014 Jan 31;588(3):503-8. doi: 10.1016/j.febslet.2013.12.016. Epub 2013 Dec 24.

Authors

Hui Wang¹, Bin Wang², Qing Liao², Hongying An², Weidong Li¹, Xuejun Jin¹, Shuzhong Cui³, Liang Zhao⁴

Affiliations

¹ Department of Medical Oncology, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China.
² Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
³ Department of Hepatobiliary Surgery, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China.
⁴ Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. Electronic address: liangsmu@gmail.com.

PMID: 24374343
DOI: 10.1016/j.febslet.2013.12.016

Abstract

RhoGDI (Rho GDP-dissociation inhibitor alpha, or RhoGDIα) was identified as a regulator of Rho GTPases, but its role in cancer remains controversial. In this study, increased expression of RhoGDI was detected in hepatocellular carcinoma (HCC) cell lines and tissues with highly metastatic potential. RhoGDI overexpression correlated with postoperative distant metastasis. Enforced expression of RhoGDI in HCC cells significantly enhanced cell proliferation and migration. Conversely, knockdown of RhoGDI caused an inhibition of the aggressive phenotypes of HCC cells. Furthermore, RhoGDI up-regulated Rho, but not Rac, and enhanced PI3K/AKT and MAPK pathway activity. Our findings suggest that RhoGDI overexpression is a predictor of distant metastasis and plays an important role in the progression of HCC.

Keywords: Hepatocellular carcinoma; Neoplasm metastasis; Rho GDP-dissociation inhibitor alpha; Signal transduction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Cell Line, Tumor
Cell Movement / genetics
Cell Proliferation*
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Liver Neoplasms / genetics*
Liver Neoplasms / metabolism
Liver Neoplasms / pathology
Neoplasm Metastasis / genetics
Prognosis
Signal Transduction
rac GTP-Binding Proteins / metabolism
rho GTP-Binding Proteins / metabolism
rho Guanine Nucleotide Dissociation Inhibitor alpha / genetics*
rho Guanine Nucleotide Dissociation Inhibitor alpha / metabolism
rho-Associated Kinases / metabolism

Substances

rho Guanine Nucleotide Dissociation Inhibitor alpha
rho-Associated Kinases
rac GTP-Binding Proteins
rho GTP-Binding Proteins