title: Expression of Ep-CAM shifts the state of cadherin-mediated adhesions from strong to weak.
abstract: Various adhesion molecules play an important role in defining cell fate and maintaining tissue integrity. Therefore, cross-signaling between adhesion receptors should be a common phenomenon to support the orchestrated changes of cells' connections to the substrate and to the neighboring cells during tissue remodeling. Recently, we have demonstrated that the epithelial cell adhesion molecule Ep-CAM negatively modulates cadherin-mediated adhesions in direct relation to its expression levels. Here, we used E-cadherin/alpha-catenin chimera constructs to define the site of Ep-CAM's negative effect on cadherin-mediated adhesions. Murine L-cells transfected with either E-cadherin/alpha-catenin fusion protein, or E-cadherin fused to the carboxy-terminal half of alpha-catenin, were subsequently supertransfected with an inducible Ep-CAM construct. Introduction of Ep-CAM altered the cell's morphology, weakened the strength of cell-cell interactions, and decreased the cytoskeleton-bound fraction of the cadherin/catenin chimeras in both cell models. Furthermore, expression of Ep-CAM induced restructuring of F-actin, with changes in thickness and orientation of the actin filaments. The results showed that Ep-CAM affects E-cadherin-mediated adhesions without involvement of beta-catenin by disrupting the link between alpha-catenin and F-actin. The latter is likely achieved through remodeling of the actin cytoskeleton by Ep-CAM, possibly through pp120.
authors.affiliation: Department of Pathology, Leiden University Medial Center, Leiden, The Netherlands.
authors.forename: Manon J
authors.initials: MJ
authors.lastname: Winter
authors.forename: Bas
authors.initials: B
authors.lastname: Nagelkerken
authors.forename: Alexander E E
authors.initials: AE
authors.lastname: Mertens
authors.forename: Hellen A M
authors.initials: HA
authors.lastname: Rees-Bakker
authors.forename: Inge H
authors.initials: IH
authors.lastname: Briaire-de Bruijn
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Litvinov
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D048429:Cell Size; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D000071858:Epithelial Cell Adhesion Molecule; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D051178:alpha Catenin
chemical_list: D000951:Antigens, Neoplasm; C495273:CTNNA1 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; D000071858:Epithelial Cell Adhesion Molecule; D011993:Recombinant Fusion Proteins; D051178:alpha Catenin