EpCAM contributes to formation of functional tight junction in the intestinal epithelium by recruiting claudin proteins

Dev Biol. 2012 Nov 15;371(2):136-45. doi: 10.1016/j.ydbio.2012.07.005. Epub 2012 Jul 20.


Tight junctions (TJs) connect epithelial cells and form a semipermeable barrier that only allows selective passage of ions and solutes across epithelia. Here we show that mice lacking EpCAM, a putative cell adhesion protein frequently overexpressed in human cancers, manifest intestinal barrier defects and die shortly after birth as a result of intestinal erosion. EpCAM was found to be highly expressed in the developing intestinal epithelium of wild-type mice and to localize to cell-cell junctions including TJs. Claudin-7 colocalized with EpCAM at cell-cell junctions, and the two proteins were found to associate with each other. Claudins 2, 3, 7, and 15 were down-regulated in the intestine of EpCAM mutant mice, with claudin-7 being reduced to undetectable levels. TJs in the mutant intestinal epithelium were morphologically abnormal with the network of TJ strands scattered and dispersed. Finally, the barrier function of the intestinal epithelium was impaired in the mutant animals. These results suggest that EpCAM contributes to formation of intestinal barrier by recruiting claudins to cell-cell junctions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Claudin-3 / genetics
  • Claudin-3 / metabolism
  • Claudins / genetics
  • Claudins / metabolism*
  • Down-Regulation
  • Epithelial Cell Adhesion Molecule
  • Intestinal Mucosa / embryology
  • Intestinal Mucosa / metabolism*
  • Mice
  • Mice, Knockout
  • Tight Junctions / metabolism*


  • Antigens, Neoplasm
  • Cell Adhesion Molecules
  • Claudin-3
  • Claudins
  • Cldn2 protein, mouse
  • Cldn3 protein, mouse
  • Cldn7 protein, mouse
  • Epithelial Cell Adhesion Molecule
  • claudin 15