Kuo-Chang Wen1, Pi-Lin Sung1, Yu-Ting Chou2, Chih-Ming Pan3, Peng-Hui Wang4, Oscar Kuang-Sheng Lee5, Cheng-Wen Wu6. 1. Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei 112, Taiwan; Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 112, Taiwan; Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei 112, Taiwan. 2. Department of Life Science and Institute of Biotechnology, National Tsing-Hua University, HsinChu 300, Taiwan. 3. Center for Cell Therapy, Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan. 4. Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei 112, Taiwan; Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 112, Taiwan; Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei 112, Taiwan. Electronic address: phwang@vghtpe.gov.tw. 5. Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei 112, Taiwan; Stem Cell Research Center, National Yang-Ming University, Taipei 112, Taiwan; Taipei City Hospital, Taipei 103, Taiwan; Department of Medical Research & Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei 112, Taiwan. Electronic address: DAV47@tpech.gov.tw. 6. Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei 112, Taiwan; Institute of Biomedical Science, Academia Sinica, Taipei 115, Taiwan. Electronic address: cwwu@ym.edu.tw.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Mitchell Acland; Georgia Arentz; Max Mussared; Fergus Whitehead; Peter Hoffmann; Manuela Klingler-Hoffmann; Martin K Oehler Journal: Front Oncol Date: 2020-12-15 Impact factor: 6.244
Authors: N Derderian; V Pereira-Prado; M Hernandez; M Isiordia-Espinoza; M Arocena; R González-González; O Tremillo-Maldonado; M Meleti; N Molina-Frechero; R Bologna-Molina Journal: Med Oral Patol Oral Cir Bucal Date: 2022-09-01