LATS2-mediated YAP1 phosphorylation is involved in HCC tumorigenesis.

ABSTRACT

YAP (yes-associated protein) is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes, including proliferation and apoptosis. Although YAP plays an important role in various tumors, the underlying mechanism in hepatocellular carcinoma (HCC) tumorigenesis remains unclear. In this study, we observed that the LATS2 was highly expressed in Bel-7402 and HepG2 cell lines, and LATS2 protein level was negatively correlated with YAP1 in HCC cells. And then, we inhibited LATS2 expression by transfecting with siRNA. Western blot and Immunofluorescent staining analysis demonstrated that LATS2 inhibition decreased the dephosphorylation of YAP1 protein and promoted YAP1 nuclear accumulation in HCC cells. Moreover, Immunoprecipitation assay results also indicated that Yap binds directly to TEAD2 and LATS2 inhibition-mediated dephosphorylation increased the YAP1/TEAD2 association, leading to YAP1/TEAD2 transcriptional activation, which in turn upregulated cell invasion in HCC cells. Taken together, our current data indicated a new regulatory mechanism of YAP1 by the LATS2-mediated phosphorylation that was involved in HCC tumorigenesis.