ARHGEF11 promotes proliferation and epithelial-mesenchymal transition of hepatocellular carcinoma through activation of β-catenin pathway.

Abstract

Rho guanine nucleotide exchange factor 11 (ARHGEF11) has been proved to promote tumor metastasis in glioblastoma and ovarian carcinoma. However, the role of ARHGEF11 in hepatocellular carcinoma (HCC) progression is largely unknown. Here, we found that ARHGEF11 was upregulated in HCC samples and highly metastatic hepatoma cell lines. Knockdown of ARHGEFF11 inhibited the cell proliferation and invasion in both HCCLM3 and SKHEP1 cell lines. Subsequent mechanistic investigation showed that downregulation of ARHGEF11 significantly attenuated β-catenin nuclear translocation, thereafter repressed the expression of ZEB1 and cyclinD1, finally contributing to inhibition of epithelial-mesenchymal transition (EMT) and cell cycle arrest. Moreover, high levels of ARHGEF11 were found to be associated with shorter disease free and overall survival. A prognostic nomogram model that integrated ARHGEF11, tumor size and BCLC classification showed good performance in predicting clinical outcomes of HCC patients. Overall, this study demonstrated that ARHGEF11 could promote proliferation and metastasis of HCC via activating β-catenin pathway, suggesting that ARHGEF11 might serve as a potential prognostic biomarker for HCC.