The Elongator is a complex with multiple subunits (Elp1-Elp6) which promotes transcript elongation and protein translation. In this study, we investigated the effects of Elongator on the migration and invasion of HCC cells as well as the underlying mechanisms. We showed that overexpression of Elp3 or Elp4 promoted the migration and invasion of HCC cells, which was abolished when either Elp3 or Elp4 was silenced. The expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 were enhanced by phosphorylation of AKT. Elongator-driven migration and invasion and the expression of MMP-2 and MMP-9 were reduced in HCC cells treated with AKT inhibitor LY294002. Depletion of Elp3 also reduced the phosphorylation of AKT induced by growth factors. In vivo assay of lung metastasis in mice demonstrated that overexpression of Elp3 increased tumor nodules metastatic to lung. Importantly, Elp3 was up-regulated in human HCC tissues, which was correlated with the phosphorylation of AKT and expression of MMP-2. Collectively, these results suggested that Elongator activated migration and invasion of HCC cells by promoting the expression of MMP-2 and MMP-9 through the PI3K/AKT signaling pathway. Our work suggests that Elongator might be a potential marker which promotes the metastasis of HCC.
Keywords: AKT; Elp3; Elp4; hepatocellular carcinoma; invasion; migration.