hPCL3s Promotes Hepatocellular Carcinoma Metastasis by Activating β-Catenin Signaling

Cancer Research
Zhen CaiDong Xie

Abstract

Two isoforms of human Polycomb-like 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 β-catenin destruction complex, inhibited β-catenin degradation, and activated β-catenin/T-cell factor signaling. Downstream of the β-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 β-catenin/IL6 pathway.Significance: hPCL3s has an oncogenic role in hepatocellular carcinoma by activating the β-catenin/IL6 signaling axis to promote metastasis. Cancer Res; 78(10); 2536-49. ©2018 AACR.

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Citations

Sep 15, 2019·Cellular Oncology (Dordrecht)·Chao SongWenhui Lou
Nov 30, 2018·Molecular Medicine Reports·Li DongRuifang Guo
Jun 27, 2020·Cancer Science·Chenxi ZhongWentao Fang
May 26, 2020·Scandinavian Journal of Gastroenterology·Haixiao WangZekuan Xu
Apr 8, 2020·Oncotarget·Souhila AbdelfettahDominique Leprince
Dec 7, 2019·Journal of the Chinese Medical Association : JCMA·Yueh ChienChien-Ying Wang
Jun 16, 2021·Experimental Cell Research·Shi XiaoyunXin Haiguang
Jul 17, 2021·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Xiujuan Zhao, Xudong Wu
Dec 4, 2021·Journal of Experimental & Clinical Cancer Research : CR·Hussein GhamlouchGareth J Morgan

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