Overexpression of RAS-Association Domain Family 6 (RASSF6) Inhibits Proliferation and Tumorigenesis in Hepatocellular Carcinoma Cells

Ras-association domain family 6 (RASSF6), a member of the RASSF family, is frequently downregulated in various types of cancer. However, the roles of RASSF6 in human hepatocellular carcinoma (HCC) are still unclear. In this study, we investigated the biological functions and related molecular mechanisms in HCC. Our results found that RASSF6 is expressed in low amounts in HCC tissues and cell lines. Overexpression of RASSF6 obviously inhibited the proliferation, invasion, and EMT process in HCC cells. Furthermore, overexpression of RASFF6 greatly downregulated the protein levels of phosphorylated focal adhesion kinase (FAK), MMP-2, and MMP-9 in HepG2 cells. Last, overexpression of RASFF6 significantly attenuated tumor growth in Balb/c nude mice. In conclusion, the present study revealed that RASFF6 can inhibit the proliferation, invasion, and migration of HCC cells both in vivo and in vitro. These inhibitory effects are through suppressing FAK phosphorylation, leading to decreased MMP-2/9 expression. RASFF6 is therefore a potential therapeutic target for treating HCC.