KCTD11 inhibits growth and metastasis of hepatocellular carcinoma through activating Hippo signaling
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Rongliang Tong1,2,*, Beng Yang1,3,*, Heng Xiao4,*, Chuanhui Peng1,2, Wendi Hu1,2, Xiaoyu Weng1,2, Shaobing Cheng1,2, Chengli Du2, Zhen Lv1, Chaofeng Ding1, Lin Zhou2,5, Haiyang Xie2,5, Jian Wu1,5 and Shusen Zheng1,2,5
1Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China
2Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310000, China
3Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou 310000, China
4Department of Hepatobiliary Surgery, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China
5The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310000, China
*These authors have contributed equally to this work
Jian Wu, email: [email protected]
Shusen Zheng, email: [email protected]
Keywords: KCTD11, hepatocellular carcinoma, Hippo pathway, p21, cell adhesion
Received: June 14, 2016 Accepted: March 29, 2017 Published: April 17, 2017
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.
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