Rab11a regulates MMP2 expression by activating the PI3K/AKT pathway in human hepatocellular carcinoma cells.

As a member of the Rab GTPase family, Rab11a plays an important role in vesicle transport and tumor progression. However, it is not clear whether it can also be used as an oncoprotein in hepatocellular carcinoma (HCC). In this study, database and immunohistochemical analyses showed that Rab11a was highly expressed in HCC tissues, and associated with poor clinical prognosis. Rab11a overexpression promoted the proliferation, migration, invasion, and anti-apoptosis of human HCC cell lines, MHCC-97H and HCC-LM3, whereas the downregulation of Rab11a inhibited these biological tumor activities. Nude mice xenograft demonstrated that Rab11a had a positive effect on the growth of hepatocellular carcinoma cells in vivo. Further studies found that the PI3K/AKT pathway and matrix metalloproteinase 2 (MMP2) upregulation can be activated by over-expression of Rab11a. However, MMP2 upregulation induced by Rab11a can be inhibited by the PI3K/AKT pathway inhibitor, LY294002. Altogether, our study established for the first time that Rab11a can play a pro-cancer role in HCC, as a novel oncoprotein, by activating the PI3K/AKT pathway to regulate MMP2 expression.