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.
Department of Life Science and Institute of Biotechnology, National Tsing-Hua University, HsinChu 300, Taiwan.
Gynecol Oncol. 2018 Feb;148(2):383-392. doi: 10.1016/j.ygyno.2017.11.033. Epub 2017 Dec 6.
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.
EpCAM 是一种跨膜糖蛋白，在子宫内膜组织中作为上皮标志物发挥作用。然而，EpCAM 与子宫内膜癌（EC）之间的相关性尚不清楚。
本研究探讨了 EpCAM 与 EC 之间的关联。免疫组织化学染色和生物信息学分析揭示了低 EpCAM 表达的临床重要性。通过体外 Transwell 侵袭实验和体内原位子宫内肿瘤注射模型研究了表达低 EpCAM 水平的细胞的迁移能力。使用 Connectivity MAP 来鉴定有效抑制低 EpCAM 表达细胞的药物。
根据免疫组化分析结果，低 EpCAM 表达与子宫内膜样 EC 患者的晚期和淋巴结转移有关，而高 EpCAM 表达有利于生存。EpCAM 沉默促进细胞侵袭，而 EpCAM 在 EpCAM 沉默的 EC 细胞中的重新表达减弱了它们的侵袭性。在原位子宫植入模型中抑制 EpCAM 促进了 EC 细胞的淋巴结转移。根据定量 PCR 和启动子报告分析，雌激素受体 α 信号通过增强其启动子活性来调节 EpCAM 的表达。如 Connectivity MAP 分析所示，transamin 抑制了 EpCAM 沉默的 EC 细胞的侵袭性。
EpCAM 的缺失可能会增加 EC 的恶性程度，这些发现为 EpCAM 在 EC 患者中的预后作用提供了新的见解。
