title: The cell-cell adhesion molecule EpCAM interacts directly with the tight junction protein claudin-7.
abstract: We recently described that in the metastasizing rat pancreatic carcinoma line BSp73ASML the cell-cell adhesion molecule EpCAM, CD44 variant isoforms and the tetraspanins D6.1A and CD9 form a complex that is located in glycolipid-enriched membrane microdomains. This complex contains, in addition, an undefined 20 kDa protein. As such complex formation influenced cell-cell adhesion and apoptosis resistance, it became of interest to identify the 20 kDa polypeptide. This 20 kDa protein, which co-precipitated with EpCAM in BSp73ASML lysates, was identified as the tight junction protein claudin-7. Correspondingly, an association between EpCAM and claudin-7 was noted in rat and human tumors and in non-transformed tissues of the gastrointestinal tract. Co-localization of the two molecules was most pronounced at basolateral membranes, but was also observed in tight junctions. Evidence for direct protein-protein interactions between EpCAM and claudin-7 was obtained by co-immunoprecipitation after treatment of tumor cells with a membrane-permeable chemical cross-linker. The complex, which is located in glycolipid-enriched membrane microdomains, is not disrupted by partial cholesterol depletion, but claudin-7 phosphorylation is restricted to the localization in glycolipid-enriched membrane microdomains. This is the first report on an association between EpCAM and claudins in both non-transformed tissues and metastasizing tumor cell lines.
authors.affiliation: Department of Tumor Progression and Tumor Defense, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Ladwein
authors.forename: Ulrich-Frank
authors.initials: UF
authors.lastname: Pape
authors.forename: Dirk-Steffen
authors.initials: DS
authors.lastname: Schmidt
authors.forename: Martina
authors.initials: M
authors.lastname: Schnölzer
authors.forename: Sabine
authors.initials: S
authors.lastname: Fiedler
authors.forename: Lutz
authors.initials: L
authors.lastname: Langbein
authors.forename: Werner W
authors.initials: WW
authors.lastname: Franke
authors.forename: Gerhard
authors.initials: G
authors.lastname: Moldenhauer
authors.forename: Margot
authors.initials: M
authors.lastname: Zöller
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D057167:Claudins; D004386:Duodenum / Q000378:metabolism / Q000648:ultrastructure; D000071858:Epithelial Cell Adhesion Molecule; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism*; D008854:Microscopy, Electron; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D051381:Rats; D019108:Tight Junctions / Q000502:physiology*
chemical_list: D000951:Antigens, Neoplasm; C112697:CD44v6 antigen; C473255:CLDN7 protein, human; D015815:Cell Adhesion Molecules; D057167:Claudins; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D008565:Membrane Proteins