Proper E‐cadherin membrane location in colon requires Dab2 and it modifies by inflammation and cancer. Issue 2 (2nd July 2020)

• Record Type: Journal Article
• Authors: Vazquez‐Carretero, María D.; García‐Miranda, Pablo; Balda, María S.; Matter, Karl; Ilundáin, Anunciación A.; Peral, María J.
• Is Part Of: Journal of cellular physiology. Volume 236:Issue 2(2021)
• Page Start: 1083
• Page End: 1093
• Publication Date: 2020-07-02
• Subjects: cancer -- colon -- Dab2 -- E‐cadherin -- inflammation -- junctions; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.29917
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: 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. Abstract : Epithelial Dab2/E‐cadherin colocalization increases at initial stages of colon inflammation. Pathology progression to adenocarcinoma led to disabled 2 (Dab2) reduction, even loss, and E‐cadherin internalization. Dab2 decrement preceded that of E‐cadherin. We suggest that Dab2 by inhibiting E‐cadherin internalization, stabilizes adherens junctions and its epithelial absence contributes to development of colon inflammation and cancer.