Hpcl3s Promotes Hepatocellular Carcinoma Metastasis By Activating Beta-Catenin Signaling

Two isoforms of human Polycomblike protein 3 (hPCL3) have been reported as components of the nuclear Polycomb repressive complex 2 (PRC2), with the short isoform (hPCL3s) showing a dominant cytoplasmic localization. The function of cytoplasmic hPCL3s has, however, not been addressed. In this study, we report that hPCL3s is upregulated in clinical hepatocellular carcinoma (HCC) samples and its expression correlated with HCC clinical features. hPCL3s positively regulated the migration, invasion, and metastasis of HCC cells. hPCL3s interacted with components of the cytoplasmic beta-catenin destruction complex, inhibited beta-catenin degradation, and activated beta-catenin/T-cell factor signaling. Downstream of the beta-catenin cascade, IL6 mediated the motility-promoting functions of hPCL3s. Forced expression of hPCL3s in the liver of a HCC mouse model promoted tumorigenesis and metastasis. Taken together, these data show that hPCL3s promotes the metastasis of HCC by activating the -catenin/IL6 pathway.Significance: hPCL3s has an oncogenic role in hepatocellular carcinoma by activating the beta-catenin/IL6 signaling axis to promote metastasis. (C) 2018 AACR.