High expression of CTHRC1 promotes EMT of epithelial ovarian cancer (EOC) and is associated with poor prognosis

// Minzhi Hou 1, 3, * , Zhiqiang Cheng 2, * , Hongwei Shen 3, * , Shanyang He 3 , Yang Li 1 , Yunping Pan 4 , Chongjin Feng 4 , Xinlin Chen 5 , Yang Zhang 6 , Millicent Lin 7 , Liantang Wang 1 , Zunfu Ke 1 1 Department of Pathology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 2 Department of Pathology, ShenZhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, P.R. China 3 Department of Gynecology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 4 Department of Stomatology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 5 Department of Preventive Medicine and Biostatistics, School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, P.R. China 6 Biomedical Engineering, University of Texas at El Paso, El Paso, Texas, USA 7 Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging (CIMI), California NanoSystems Institute (CNSI), University of California, Los Angeles, California, USA * These authors have contributed equally to this work Correspondence to: Zunfu Ke, e-mail: kezunfu@126.com Keywords: CTHRC1, epithelial-mesenchymal transition, epithelial ovarian cancer, β-catenin Received: May 04, 2015      Accepted: September 21, 2015      Published: October 03, 2015 ABSTRACT Collagen triple helix repeat-containing 1 (CTHRC1) is aberrantly overexpressed in multiple malignant tumors. However, the expression characteristics and function of CTHRC1 in epithelial ovarian cancer (EOC) remain unclear. We found that CTHRC1 expression was up-regulated in the paraffin-embedded EOC tissues compared to borderline or benign tumor tissues. CTHRC1 expression was positively correlated with tumor size ( p = 0.008), menopause ( p = 0.037), clinical stage ( p = 0.002) and lymph node metastasis ( p < 0.001) and was also an important prognostic factor for the overall survival of EOC patients, as revealed by Kaplan-Meier analysis. CTHRC1 increased the invasive capabilities of EOC cells in vitro by activating the Wnt/β-catenin signaling pathway. We showed that ectopic transfection of CTHRC1 in EOC cells up-regulated the expression of EMT markers such as N-cadherin and vimentin, and EMT-associated transcriptional factor Snail. Knockdown of CTHRC1 expression in EOC cells resulted in down-regulation of N-cadherin, vimentin, Snail and translocation of β-catenin. Collectively, CTHRC1 may promote EOC metastasis through the induction of EMT process and serve as a potential biomarker for prognosis as well as a target for therapy.