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Proper E‐cadherin membrane location in colon requires Dab2 and it modifies by inflammation and cancer
Author(s) -
VazquezCarretero María D.,
GarcíaMiranda Pablo,
Balda María S.,
Matter Karl,
Ilundáin Anunciación A.,
Peral María J.
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29917
Subject(s) - cadherin , inflammation , colorectal cancer , cancer , cancer research , microbiology and biotechnology , biology , medicine , immunology , biochemistry , cell
We reported that Disabled‐2 (Dab2) is located at the apical membrane in suckling rat intestine. Here, we discovered that, in colon of suckling and adult mouse and of adult human, Dab2 is only at lateral crypt cell membrane and colocalized with E‐cadherin. Dab2 depletion in Caco‐2 cells led to E‐cadherin internalization indicating that its membrane location requires Dab2. In mice, we found that 3 days of dextran sulfate sodium‐induced colitis increased Dab2/E‐cadherin colocalization, which was decreased as colitis progressed to 6 and 9 days. In agreement, Dab2/E‐cadherin colocalization increased in human mild and severe ulcerative colitis and in polyps, being reduced in colon adenocarcinomas, which even showed epithelial Dab2 absence and E‐cadherin delocalization. Epithelial Dab2 decrement preceded that of E‐cadherin. We suggest that Dab2, by inhibiting E‐cadherin internalization, stabilizes adherens junctions, and its absence from the epithelium may contribute to development of colon inflammation and cancer.