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

Bernardina T. F. van der Gun, Lieuwe J. Melchers, Marcel H. J. Ruiters, Lou F. M. H. de Leij, Pamela M. J. McLaughlin, Marianne G. Rots*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

216 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1913-1921
Number of pages9
JournalCARCINOGENESIS
Volume31
Issue number11
DOIs
Publication statusPublished - Nov-2010

Keywords

  • CELL-ADHESION-MOLECULE
  • CANCER STEM-CELLS
  • DISSEMINATED TUMOR-CELLS
  • EP-CAM EXPRESSION
  • EPITHELIAL GLYCOPROTEIN-2 PROMOTER
  • CONGENITAL TUFTING ENTEROPATHY
  • BREAST-CANCER
  • LYMPH-NODES
  • DNA METHYLATION
  • OVARIAN-CANCER

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