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Proper E-cadherin membrane location in colon requires Dab2 and it modifies by inflammation and cancer

Vazquez-Carretero, MD; Garcia-Miranda, P; Balda, MS; Matter, K; Ilundain, AA; Peral, MJ; (2021) Proper E-cadherin membrane location in colon requires Dab2 and it modifies by inflammation and cancer. Journal of Cellular Physiology , 236 (2) pp. 1083-1093. 10.1002/jcp.29917. Green open access

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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.

Type: Article
Title: Proper E-cadherin membrane location in colon requires Dab2 and it modifies by inflammation and cancer
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/jcp.29917
Publisher version: http://dx.doi.org/10.1002/jcp.29917
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: cancer, colon, Dab2, E-cadherin, inflammation, junctions,
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10105364
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