EpCAM is involved in maintenance of the murine embryonic stem cell phenotype

Stem Cells. 2009 Aug;27(8):1782-91. doi: 10.1002/stem.97.


Epithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein that is expressed on subsets of normal epithelia, numerous stem- and progenitor-type cells, and most carcinomas and highly overexpressed on cancer-initiating cells. The role of EpCAM in early development, particularly in stem-like cells, has remained unclear. Here, we show that the maintenance of self-renewal in murine embryonic stem (ES) cells depends on the high-level expression of EpCAM. Cultivation of ES cells under differentiation conditions in the absence of leukemia inhibitory factor (LIF) caused down-regulation of EpCAM along with decreased expression of cellular myelocytomatosis oncogene (c-Myc), Sex-determining region Y-Box 2, Octamer 3/4 (Oct3/4), and Stat3. As a consequence ES cells were morphologically differentiated and ceased to proliferate. RNA interference-mediated inhibition of EpCAM expression under self-renewal conditions resulted in quantitatively decreased proliferation, decreased Oct3/4, SSEA-1, and c-Myc expression, and diminished alkaline phosphatase activity. Conversely, exogenous expression of EpCAM partially compensated for the requirement of ES cells for LIF to retain a stem cell phenotype. Thus, murine EpCAM is a transmembrane protein, which is essential but by itself is not sufficient for maintenance of the ES cell phenotype.

MeSH terms

  • Animals
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Cell Adhesion Molecules / antagonists & inhibitors
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Differentiation / physiology
  • Cell Line, Tumor
  • Down-Regulation
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Epithelial Cell Adhesion Molecule
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Humans
  • Leukemia Inhibitory Factor / metabolism
  • Mice
  • Microscopy, Confocal
  • Phenotype
  • RNA, Small Interfering / genetics
  • Signal Transduction
  • Transfection


  • Antigens, Neoplasm
  • Cell Adhesion Molecules
  • Epithelial Cell Adhesion Molecule
  • Leukemia Inhibitory Factor
  • Lif protein, mouse
  • RNA, Small Interfering