Epithelial-mesenchymal transition and nuclear β-catenin induced by conditional intestinal disruption of Cdh1 with Apc is E-cadherin EC1 domain dependent.Reportar como inadecuado




Epithelial-mesenchymal transition and nuclear β-catenin induced by conditional intestinal disruption of Cdh1 with Apc is E-cadherin EC1 domain dependent. - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Reference: Matheson, J, Bühnemann, C, Carter, EJ et al., (2016). Epithelial-mesenchymal transition and nuclear β-catenin induced by conditional intestinal disruption of Cdh1 with Apc is E-cadherin EC1 domain dependent. Oncotarget.Citable link to this page:

 

Epithelial-mesenchymal transition and nuclear β-catenin induced by conditional intestinal disruption of Cdh1 with Apc is E-cadherin EC1 domain dependent.

Abstract: Two important protein-protein interactions establish E-cadherin (Cdh1) in the adhesion complex; homophilic binding via the extra-cellular (EC1) domain and cytoplasmic tail binding to β-catenin. Here, we evaluate whether E-cadherin binding can inhibit β-catenin when there is loss of Adenomatous polyposis coli (APC) from the β-catenin destruction complex. Combined conditional loss of Cdh1 and Apc were generated in the intestine, intestinal adenoma and adenoma organoids. Combined intestinal disruption (Cdh1fl/flApcfl/flVil-CreERT2) resulted in lethality, breakdown of the intestinal barrier, increased Wnt target gene expression and increased nuclear β-catenin localization, suggesting that E-cadherin inhibits β-catenin. Combination with an intestinal stem cell Cre (Lgr5CreERT2) resulted in ApcΔ/Δ recombination and adenoma, but intact Cdh1fl/fl alleles. Cultured ApcΔ/ΔCdh1fl/fl adenoma cells infected with adenovirus-Cre induced Cdh1fl/fl recombination (Cdh1Δ/Δ), disruption of organoid morphology, nuclear β-catenin localization, and cells with an epithelial-mesenchymal phenotype. Complementation with adenovirus expressing wild-type Cdh1 (Cdh1-WT) rescued adhesion and β-catenin membrane localization, yet an EC1 specific double mutant defective in homophilic adhesion (Cdh1-MutW2A, S78W) did not. These data suggest that E-cadherin inhibits β-catenin in the context of disruption of the APC-destruction complex, and that this function is also EC1 domain dependent. Both binding functions of E-cadherin may be required for its tumour suppressor activity.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Publisher's versionDate of acceptance:2016-08-08 Funder: Rhodes Trust   Funder: Cancer Research UK   Notes:Copyright [at] 2016 Impact Journals, LLC. All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.

Bibliographic Details

Publisher: Impact Journal

Publisher Website: http://www.impactjournals.com/

Journal: Oncotargetsee more from them

Publication Website: http://www.impactjournals.com/oncotarget/

Issue Date: 2016-08Identifiers

Doi: https://doi.org/10.18632/oncotarget.11513

Issn: 1949-2553

Uuid: uuid:ca953b62-7592-4e09-b7f0-0cae0d0e55da

Urn: uri:ca953b62-7592-4e09-b7f0-0cae0d0e55da

Pubs-id: pubs:640863 Item Description

Type: journal-article;

Language: eng

Version: Publisher's versionKeywords: Apc E-cadherin adhesion complex intestine β-catenin

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Autor: Matheson, J - - - Bühnemann, C - - - Carter, EJ - Oxford, MSD, Biochemistry - - - Barnes, D - Oxford, MSD, Pathology Dunn School

Fuente: https://ora.ox.ac.uk/objects/uuid:ca953b62-7592-4e09-b7f0-0cae0d0e55da



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