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CTHRC1的高表达促进上皮性卵巢癌(EOC)的上皮-间质转化,并与不良预后相关。

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

作者信息

Hou Minzhi, Cheng Zhiqiang, Shen Hongwei, He Shanyang, Li Yang, Pan Yunping, Feng Chongjin, Chen Xinlin, Zhang Yang, Lin Millicent, Wang Liantang, Ke Zunfu

机构信息

Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China.

Department of Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China.

出版信息

Oncotarget. 2015 Nov 3;6(34):35813-29. doi: 10.18632/oncotarget.5358.

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.

摘要

含胶原蛋白三螺旋重复序列1(CTHRC1)在多种恶性肿瘤中异常高表达。然而,CTHRC1在上皮性卵巢癌(EOC)中的表达特征和功能仍不清楚。我们发现,与交界性或良性肿瘤组织相比,石蜡包埋的EOC组织中CTHRC1表达上调。CTHRC1表达与肿瘤大小(p = 0.008)、绝经状态(p = 0.037)、临床分期(p = 0.002)和淋巴结转移(p < 0.001)呈正相关,并且如Kaplan-Meier分析所示,也是EOC患者总生存的一个重要预后因素。CTHRC1通过激活Wnt/β-连环蛋白信号通路在体外增强EOC细胞的侵袭能力。我们发现,EOC细胞中CTHRC1的异位转染上调了N-钙黏蛋白和波形蛋白等EMT标志物以及EMT相关转录因子Snail的表达。EOC细胞中CTHRC1表达的敲低导致N-钙黏蛋白、波形蛋白、Snail表达下调以及β-连环蛋白的易位。总之,CTHRC1可能通过诱导EMT过程促进EOC转移,并作为一种潜在的预后生物标志物以及治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36c8/4742143/8b74983328b8/oncotarget-06-35813-g001.jpg

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