Rab23 Promotes Hepatocellular Carcinoma Cell Migration Via Rac1/TGF-ß Signaling.

ABSTRACT

Rab23 is a member of Ras-related small GTPase family, which plays a critical role in the progression of wide range of tumors. However, its biological function in hepatocellular carcinoma still remains unclear. Here, we investigated the effects of Rab23 on proliferation and migration in hepatocellular carcinoma cell and its potential mechanisms. We found over-expression of Rab23 promoted the Hep3B hepatocellular carcinoma cell migration, which could be reversed by Rab23 silencing. Rab23 induced Rac1 activation and followed progression of epithelial-mesenchymal transition (EMT) along with upregulation of N-cadherin, snail as well as vimentin and downregulation of E-cadherin via upregulating Transforming Growth Factor-ß (TGF-ß). Silencing Rac1 significantly attenuated Rab23-induced HepG2 migration and TGF-ß. Moreover, knockdown of TGF-ß effectively attenuated Rab23-induced EMT. Taken together, we demonstrated a mechanistic cascade of Rab23 enhangcing Rac1 activation and subsequent TGF-ß expression, leading to hepatocellular carcinoma cell migration.