Epithelial to mesenchymal transition is involved in ethanol promoted hepatocellular carcinoma cells metastasis and stemness

Abstract

Hepatocellular Carcinoma (HCC) is a malignant tumor with high rate of relapse and metastasis. Ethanol is a well-known risk factor for HCC; it promotes the progression and aggressiveness of HCC. However, the underlying mechanism remains unclear. In clinic studies, we showed that alcohol consumption is positively correlated with TNM stage and vessel invasion; HCC patients with chronic drinking history had faster progression rate and poorer prognosis compared to non-drinkers. In experimental models, ethanol exposure enhanced the metastasis, and invasion of HCC cells. Ethanol exposure increased cancer stem cells (CSC) population and enhanced stemness of HCC cells in vitro and in vivo. Mechanically, we found that ethanol exposure induced epithelial to mesenchymal transition (EMT) through activating Wnt/β-catenin signaling pathway in HCC cells. We further demonstrated that β-catenin siRNA or salinomycin (an inhibitor of Wnt/β-catenin pathway) partially rescued ethanol-induced EMT. In conclusion, this study suggested that ethanol exposure promotes the metastasis and stemness of HCC cells by inducing EMT.