EpCAM: Structure and function in health and disease

Abstract

Injection of tumor cells in mice more than 30 years ago resulted in the discovery of an epithelial antigen, later defined as a cell adhesion molecule (EpCAM). Although EpCAM has since evoked significant interest as a target in cancer therapy, mechanistic insights on the functions of this glycoprotein have been emerging only very recently. This may have been caused by the multitude of functions attributed to the glycoprotein, its localization at different subcellular sites and complex posttranslational modifications. Here, we review how EpCAM modifies cell-cell contact adhesion strength and tissue plasticity, and how it regulates cell proliferation and differentiation. Major knowledge derived from human diseases will be highlighted: Mutant EpCAM that is absent from the cell surface leads to fatal intestinal abnormalities (congenital tufting enteropathy). EpCAM-mediated cell proliferation in cancer may result from signaling (i) via regulated intramembrane proteolysis and/or (ii) the localization and association with binding partners in specialized membrane microdomains. New insight in EpCAM signaling will help to develop optimized cancer therapies and open new avenues in the field of regenerative medicine.

The role of epithelial cell adhesion molecule N-glycosylation on apoptosis in breast cancer cells

“…Increasing clinical evidence has confirmed that EpCAM is involved in cancer progression and is associated with a poor prognosis. [7][8][9] More evidence suggested that EpCAM played a critical factor in tumor development, progression, and metastasis. 10,11 For example, EpCAM is frequently overexpressed in patients with acute myeloid leukemia (AML), with EpCAM + leukemic cells exhibiting enhanced chemoresistance and oncogenesis.…”

Setdb1 maintains hematopoietic stem and progenitor cells by restricting the ectopic activation of nonhematopoietic genes

“…20 A mega-analysis of the gene expression database using the online software tool ExAtlas 21 revealed that derepressed genes ($2-fold) were largely nonhematopoietic genes ( Figure 3B). We compared ChIP-seq data for H3K9me3 levels with RNA-seq data in GMPs.…”

Classification of Cells with Membrane Staining and/or Fixation Based on Cellular Specific Membrane Capacitance and Cytoplasm Conductivity

“…Figure 3a shows the bright field and fluorescent images of stained PC-3 cells without fixation (GS&NF), which suggested the existence of anti-Human EpCAM Alexa Fluor 488. , which may result from the endocytosis of anti-EpCAM after binding with surface antigen EpCAM. In addition, a significant difference in σcytoplasm for GNS&NF vs. GS&NF cells was observed, further suggesting the possibility of surface antigen endocytosis and the triggering of the downstream signal pathways [26].…”