KCTD11 inhibits growth and metastasis of hepatocellular carcinoma through activating Hippo signaling.

// Rongliang Tong 1, 2, * , Beng Yang 1, 3, * , Heng Xiao 4, * , Chuanhui Peng 1, 2 , Wendi Hu 1, 2 , Xiaoyu Weng 1, 2 , Shaobing Cheng 1, 2 , Chengli Du 2 , Zhen Lv 1 , Chaofeng Ding 1 , Lin Zhou 2, 5 , Haiyang Xie 2, 5 , Jian Wu 1, 5 and Shusen Zheng 1, 2, 5 1 Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China 2 Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310000, China 3 Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou 310000, China 4 Department of Hepatobiliary Surgery, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China 5 The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310000, China * These authors have contributed equally to this work Correspondence to: Jian Wu, email: drwujian@hotmail.com Shusen Zheng, email: shusenzheng@zju.edu.cn Keywords: KCTD11, hepatocellular carcinoma, Hippo pathway, p21, cell adhesion Received: June 14, 2016      Accepted: March 29, 2017      Published: April 17, 2017 ABSTRACT A lack of effective prognostic biomarkers and molecular targets is a serious problem in hepatocellular carcinoma. KCTD11, reported as a tumor suppressor, are still not well understood. In this study, KCTD11 was found low-expressed in HCC tissues and cell lines. The HCC patients with low expression of KCTD11 suggested shorter overall survival. We found KCTD11 inhibiting cell proliferation in vitro and tumor growth in vivo , by activating p21 and repressing cycle related proteins. KCTD11 also inhibited cell adhesion by decreasing CTGF and CLDN1. We found CTGF binding COL3A1 in HCCLM3, which might lead to reduction of COL3A1 expression. KCTD11 also inhibited cell migration and invasion in HCC, by repressing MMPs and EMT. We found the tumor suppression function of KCTD11 was at least partly through activating Hippo pathway in HCC. Base on the enhanced Hippo pathway, KCTD11 could activate p21 by stabilizing p53 or promoting the MST1/ GSK3β/p21 signaling in HCC. Overall, these results suggest that KCTD11 works as a tumor suppressor and owns prognostic and therapeutic potentials in HCC.