The role of EpCAM in tumor progression and the clinical prognosis of endometrial carcinoma

EpCAM is a transmembrane glycoprotein that functions as an epithelial marker in endometrial tissues. However, the correlation between EpCAM and endometrial carcinoma (EC) is not clear. This study investigated the association between EpCAM and EC. Immunohistochemistry staining and bioinformatics anal...

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Bibliographic Details
Published in:Gynecologic oncology 2018-02, Vol.148 (2), p.383-392
Main Authors: Wen, Kuo-Chang, Sung, Pi-Lin, Chou, Yu-Ting, Pan, Chih-Ming, Wang, Peng-Hui, Lee, Oscar Kuang-Sheng, Wu, Cheng-Wen
Format: Article
Language:English
Subjects:
Endometrial cancer
EpCAM
ERα
Poor prognosis
Tumor metastasis
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Summary:EpCAM is a transmembrane glycoprotein that functions as an epithelial marker in endometrial tissues. However, the correlation between EpCAM and endometrial carcinoma (EC) is not clear. This study investigated the association between EpCAM and EC. Immunohistochemistry staining and bioinformatics analysis disclosed the clinical importance of low EpCAM expression. The migratory ability of cells expressing low EpCAM levels was studied in transwell invasion assays in vitro and an orthotopic intra-uterine tumor injection model in vivo. The Connectivity MAP was used to identify drugs that effectively inhibit cells with low EpCAM expression. According to immunohistochemistry analysis results, low EpCAM expression was associated with an advanced stage and lymph node metastasis in patients with endometrioid EC, and high EpCAM expression favored survival. EpCAM silencing promoted cell invasion, and EpCAM re-expression in EpCAM-silenced EC cells attenuated their invasiveness. EpCAM suppression in an orthotopic uterine implantation model promoted the lymph node metastasis of EC cells. According to quantitative PCR and promoter reporter analyses, estrogen receptor alpha signaling regulated EpCAM expression by enhancing its promoter activity. As shown in the Connectivity MAP analysis, transamin inhibited the invasiveness of EpCAM-silenced EC cells. The loss of EpCAM may increase the malignancy of EC, and these findings provide new insights into the prognostic role of EpCAM in patients with EC. •Downregulation of EpCAM favors a poor prognosis and cancer cell invasion of EC.•ERα-induced EpCAM expression suppresses the dissemination of EC cells.•Transamin is a potential inhibitor of highly invasive EC cells.
ISSN:0090-8258
1095-6859
DOI:10.1016/j.ygyno.2017.11.033