EpCAM in carcinogenesis: the good, the bad or the ugly

Abstract

The epithelial cell adhesion molecule (EpCAM) is a membrane glycoprotein that is highly expressed on most carcinomas and therefore of potential use as a diagnostic and prognostic marker for a variety of carcinomas. Interestingly, EpCAM is explored as target in antibody-based therapies. Recently, EpCAM has been identified as an additional marker of cancer-initiating cells. In this review, we describe the controversial biological role of EpCAM with the focus on carcinogenesis: as an adhesion molecule, EpCAM mediates homophilic adhesion interactions, which in turn might prevent metastasis. On the other hand, EpCAM abrogates E-cadherin mediated cell-cell adhesion thereby promoting metastasis. Also, upon cleavage of EpCAM, the intracellular domain functions as a part of a transcriptional complex inducing c-myc and cyclin A and E. In line with these seemingly controversial roles, EpCAM overexpression has been associated with both decreased and increased survival of patients. Similarly, either induction or downregulation of EpCAM expression lowers the oncogenic potential depending on the cell type. As epigenetic dysregulation underlies aberrant EpCAM expression, we propose epigenetic editing as a novel approach to investigate the biological role of EpCAM, expanding the options for EpCAM as a therapeutic target in cancer.

Upregulation of endogenous ICAM‐1 reduces ovarian cancer cell growth in the absence of immune cells

“…33,35 The different outcome between cDNA transfection in colon or liver cancer cells and ATF-induced ICAM-1 expression in our experiments might be explained by the difference in tumor types (colorectal/liver cancer versus ovarian cancer). Actually, multiple examples are known of genes displaying cell-context dependent seemingly controversial roles, such as EpCAM 36 or Maspin. 37 In this respect, in breast cancer cells, silencing of ICAM-1 expression by siRNA resulted in decreased tumorigenicity in vitro.…”

Increasing the Antitumor Effect of an EpCAM-Targeting Fusion Toxin by Facile Click PEGylation

“…EpCAM, also known as CD326, is a 40 kDa type I membrane glycoprotein frequently expressed in human carcinomas, and involved in cell proliferation by linking to components of the Wnt signaling pathway and regulators of the cell cycle (14,15). It initially attracted attention as a target for cancer-related immunotherapy due to its abundant expression in solid tumors, although expression in normal epithelia is low (14)(15)(16)(17), and recent studies further unveiled its association with cancer stem cells (15)(16)(17)(18)(19) and circulating tumor cells (16,18,19). Currently, several anti-EpCAM antibodies are under clinical development (15), with the human antibody adecatumumab being the most advanced candidate (20,21).…”

Increased Expression of Epithelial Cell Adhesion Molecule (EpCAM) in Rat Hepatic Tumors Induced by Diethylnitrosamine

“…EpCAM is considered as one of the stem cell markers and its expression has been identified as an additional marker of cancer-initiating cells (van der Gun et al, 2010) and was considered as hepatic stem/progenitor cells in HCCs subtype (Yamashita et al, 2009). In this study, EpCAM expression showed diffuse cytoplasmic staining in tumor cells.…”

“…It was first proposed to function as a cell adhesion molecule since it mediates homophilic adhesion interaction, which might prevent metastasis (Litvinov et al, 1994). In contrast, EpCAM has been reported to abrogate E-cadherin-mediated cell-cell adhesion, indicating that is may have a different role in some other tumor type by promoting metastasis (van der Gun et al, 2010). In humans, EpCAM-expression in liver cells was rare in early stages of liver diseases and was increasingly prominent in later stages, consistently arrayed around the periphery of cords of hepatobiliary cells (Yoon et al, 2011).…”