The cell–cell adhesion molecule EpCAM interacts directly with the tight junction protein claudin-7

M Ladwein, UF Pape, DS Schmidt, M Schnölzer… - Experimental cell …, 2005 - Elsevier
M Ladwein, UF Pape, DS Schmidt, M Schnölzer, S Fiedler, L Langbein, WW Franke
Experimental cell research, 2005Elsevier
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 …
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.
Elsevier