EpCAM homo-oligomerization is not the basis for its role in cell-cell adhesion

Sci Rep. 2018 Sep 5;8(1):13269. doi: 10.1038/s41598-018-31482-7.


Cell-surface tumor marker EpCAM plays a key role in proliferation, differentiation and adhesion processes in stem and epithelial cells. It is established as a cell-cell adhesion molecule, forming intercellular interactions through homophilic association. However, the mechanism by which such interactions arise has not yet been fully elucidated. Here, we first show that EpCAM monomers do not associate into oligomers that would resemble an inter-cellular homo-oligomer, capable of mediating cell-cell adhesion, by using SAXS, XL-MS and bead aggregation assays. Second, we also show that EpCAM forms stable dimers on the surface of a cell with pre-formed cell-cell contacts using FLIM-FRET; however, no inter-cellular homo-oligomers were detectable. Thus, our study provides clear evidence that EpCAM indeed does not function as a homophilic cell adhesion molecule and therefore calls for a significant revision of its role in both normal and cancerous tissues. In the light of this, we strongly support the previously suggested name Epithelial Cell Activating Molecule instead of the Epithelial Cell Adhesion Molecule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Cell Adhesion / physiology*
  • Cell Adhesion Molecules / metabolism
  • Cell Differentiation / physiology
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Epithelial Cell Adhesion Molecule / biosynthesis
  • Epithelial Cell Adhesion Molecule / chemistry*
  • Epithelial Cell Adhesion Molecule / genetics
  • Epithelial Cell Adhesion Molecule / metabolism*
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • HEK293 Cells
  • Humans
  • Signal Transduction
  • Spodoptera / genetics
  • Spodoptera / metabolism
  • Structure-Activity Relationship
  • X-Ray Diffraction


  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule