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DDR1 triggers epithelial cell differentiation by promoting cell adhesion through stabilization of E-cadherin

Discoidin domain receptor 1 (DDR1) promotes E-cadherin–mediated adhesion. The underlying mechanism and its significance, however, have not been elucidated. Here we show that DDR1 overexpression augmented, whereas dominant negative mutant (DN-DDR1) or knockdown of DDR1 inhibited E-cadherin localized...

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Detalles Bibliográficos
Autores principales: Yeh, Yi-Chun, Wu, Chia-Ching, Wang, Yang-Kao, Tang, Ming-Jer
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069019/
https://www.ncbi.nlm.nih.gov/pubmed/21289093
http://dx.doi.org/10.1091/mbc.E10-08-0678
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author Yeh, Yi-Chun
Wu, Chia-Ching
Wang, Yang-Kao
Tang, Ming-Jer
author_facet Yeh, Yi-Chun
Wu, Chia-Ching
Wang, Yang-Kao
Tang, Ming-Jer
author_sort Yeh, Yi-Chun
collection PubMed
description Discoidin domain receptor 1 (DDR1) promotes E-cadherin–mediated adhesion. The underlying mechanism and its significance, however, have not been elucidated. Here we show that DDR1 overexpression augmented, whereas dominant negative mutant (DN-DDR1) or knockdown of DDR1 inhibited E-cadherin localized in cell-cell junctions in epithelial cells. DDR1 changed the localization and abundance of E-cadherin, as well as epithelial plasticity, as manifested by enhancement of microvilli formation and alteration of cytoskeletal organization. DDR1 also reduced protein abundance of mesenchymal markers, whereas DN-DDR1 and sh-DDR1 showed opposite effects. These results suggest that expression of DDR1 increases epithelial plasticity. Expression of DDR1 augmented E-cadherin protein levels by decreasing its degradation rate. Photobleaching and photoconversion of E-cadherin conjugated with Eos fluorescence protein demonstrated that DDR1 increased the stability of E-cadherin on the cell membrane, whereas sh-DDR1 decreased it. Pull-down assay and expression of constitutively active or dominant-negative Cdc42 showed that DDR1 stabilized E-cadherin through inactivation of Cdc42. Altogether, our results show that DDR1 promotes cell-cell adhesion and differentiation through stabilization of E-cadherin, which is mediated by Cdc42 inactivation.
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spelling pubmed-30690192011-06-16 DDR1 triggers epithelial cell differentiation by promoting cell adhesion through stabilization of E-cadherin Yeh, Yi-Chun Wu, Chia-Ching Wang, Yang-Kao Tang, Ming-Jer Mol Biol Cell Articles Discoidin domain receptor 1 (DDR1) promotes E-cadherin–mediated adhesion. The underlying mechanism and its significance, however, have not been elucidated. Here we show that DDR1 overexpression augmented, whereas dominant negative mutant (DN-DDR1) or knockdown of DDR1 inhibited E-cadherin localized in cell-cell junctions in epithelial cells. DDR1 changed the localization and abundance of E-cadherin, as well as epithelial plasticity, as manifested by enhancement of microvilli formation and alteration of cytoskeletal organization. DDR1 also reduced protein abundance of mesenchymal markers, whereas DN-DDR1 and sh-DDR1 showed opposite effects. These results suggest that expression of DDR1 increases epithelial plasticity. Expression of DDR1 augmented E-cadherin protein levels by decreasing its degradation rate. Photobleaching and photoconversion of E-cadherin conjugated with Eos fluorescence protein demonstrated that DDR1 increased the stability of E-cadherin on the cell membrane, whereas sh-DDR1 decreased it. Pull-down assay and expression of constitutively active or dominant-negative Cdc42 showed that DDR1 stabilized E-cadherin through inactivation of Cdc42. Altogether, our results show that DDR1 promotes cell-cell adhesion and differentiation through stabilization of E-cadherin, which is mediated by Cdc42 inactivation. The American Society for Cell Biology 2011-04-01 /pmc/articles/PMC3069019/ /pubmed/21289093 http://dx.doi.org/10.1091/mbc.E10-08-0678 Text en © 2011 Yeh et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,“ “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Yeh, Yi-Chun
Wu, Chia-Ching
Wang, Yang-Kao
Tang, Ming-Jer
DDR1 triggers epithelial cell differentiation by promoting cell adhesion through stabilization of E-cadherin
title DDR1 triggers epithelial cell differentiation by promoting cell adhesion through stabilization of E-cadherin
title_full DDR1 triggers epithelial cell differentiation by promoting cell adhesion through stabilization of E-cadherin
title_fullStr DDR1 triggers epithelial cell differentiation by promoting cell adhesion through stabilization of E-cadherin
title_full_unstemmed DDR1 triggers epithelial cell differentiation by promoting cell adhesion through stabilization of E-cadherin
title_short DDR1 triggers epithelial cell differentiation by promoting cell adhesion through stabilization of E-cadherin
title_sort ddr1 triggers epithelial cell differentiation by promoting cell adhesion through stabilization of e-cadherin
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069019/
https://www.ncbi.nlm.nih.gov/pubmed/21289093
http://dx.doi.org/10.1091/mbc.E10-08-0678
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