EpCAM in carcinogenesis: the good, the bad or the ugly.
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.
van der Gun
Bernardina T F
BT
Epigenetic Editing, Department of Medical Biology, University Medical Centre Groningen, Hanzeplein 1, Groningen, TheNetherlands.
Melchers
Lieuwe J
LJ
Ruiters
Marcel H J
MH
de Leij
Lou F M H
LF
McLaughlin
Pamela M J
PM
Rots
Marianne G
MG
D000951:Antigens, Neoplasm / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D044127:Epigenesis, Genetic; D000071858:Epithelial Cell Adhesion Molecule; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule