Research Papers:
High expression of CTHRC1 promotes EMT of epithelial ovarian cancer (EOC) and is associated with poor prognosis
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Abstract
Minzhi Hou1,3,*, Zhiqiang Cheng2,*, Hongwei Shen3,*, Shanyang He3, Yang Li1, Yunping Pan4, Chongjin Feng4, Xinlin Chen5, Yang Zhang6, Millicent Lin7, Liantang Wang1, Zunfu Ke1
1Department of Pathology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China
2Department of Pathology, ShenZhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, P.R. China
3Department of Gynecology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China
4Department of Stomatology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China
5Department of Preventive Medicine and Biostatistics, School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, P.R. China
6Biomedical Engineering, University of Texas at El Paso, El Paso, Texas, USA
7Department 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: [email protected]
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.
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