Cargando…

A Novel Role for p115RhoGEF in Regulation of Epithelial Plasticity

Epithelial plasticity plays a critical role during physiological processes, such as wound healing and tissue regeneration, and dysregulation of epithelial plasticity can lead to pathological conditions, such as cancer. Cell-cell junctions are a critical feature of epithelial cells and loss of juncti...

Descripción completa

Detalles Bibliográficos
Autores principales: Kher, Swapnil S., Struckhoff, Amanda P., Alberts, Arthur S., Worthylake, Rebecca A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900421/
https://www.ncbi.nlm.nih.gov/pubmed/24465552
http://dx.doi.org/10.1371/journal.pone.0085409
_version_ 1782300690256756736
author Kher, Swapnil S.
Struckhoff, Amanda P.
Alberts, Arthur S.
Worthylake, Rebecca A
author_facet Kher, Swapnil S.
Struckhoff, Amanda P.
Alberts, Arthur S.
Worthylake, Rebecca A
author_sort Kher, Swapnil S.
collection PubMed
description Epithelial plasticity plays a critical role during physiological processes, such as wound healing and tissue regeneration, and dysregulation of epithelial plasticity can lead to pathological conditions, such as cancer. Cell-cell junctions are a critical feature of epithelial cells and loss of junctions is associated with acquisition of mesenchymal features, such as enhanced protrusion and migration. Although Rho has been implicated in regulation of junctions in epithelial cells, the role of Rho signaling in the regulation of epithelial plasticity has not been understood. We show that members of the RGS RhoGEFs family play a critical role in regulation of epithelial cell-cell junctions in breast epithelial cells. We identify a novel role for p115RhoGEF in regulation of epithelial plasticity. Loss of p115RhoGEF leads to decreased junctional E-cadherin and enhanced protrusiveness and migration. Conversely, overexpression of p115RhoGEF enhanced junctional E-cadherin and inhibited cell protrusion and migration. siRNA screen of 23 Rho effectors showed that members of the Diaphanous-Related Formin (DRF) family are required for p115RhoGEF-mediated changes in epithelial plasticity. Thus, our data indicates a novel role for p115RhoGEF in regulation of epithelial plasticity, which is dependent on Rho-DRF signaling module.
format Online
Article
Text
id pubmed-3900421
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-39004212014-01-24 A Novel Role for p115RhoGEF in Regulation of Epithelial Plasticity Kher, Swapnil S. Struckhoff, Amanda P. Alberts, Arthur S. Worthylake, Rebecca A PLoS One Research Article Epithelial plasticity plays a critical role during physiological processes, such as wound healing and tissue regeneration, and dysregulation of epithelial plasticity can lead to pathological conditions, such as cancer. Cell-cell junctions are a critical feature of epithelial cells and loss of junctions is associated with acquisition of mesenchymal features, such as enhanced protrusion and migration. Although Rho has been implicated in regulation of junctions in epithelial cells, the role of Rho signaling in the regulation of epithelial plasticity has not been understood. We show that members of the RGS RhoGEFs family play a critical role in regulation of epithelial cell-cell junctions in breast epithelial cells. We identify a novel role for p115RhoGEF in regulation of epithelial plasticity. Loss of p115RhoGEF leads to decreased junctional E-cadherin and enhanced protrusiveness and migration. Conversely, overexpression of p115RhoGEF enhanced junctional E-cadherin and inhibited cell protrusion and migration. siRNA screen of 23 Rho effectors showed that members of the Diaphanous-Related Formin (DRF) family are required for p115RhoGEF-mediated changes in epithelial plasticity. Thus, our data indicates a novel role for p115RhoGEF in regulation of epithelial plasticity, which is dependent on Rho-DRF signaling module. Public Library of Science 2014-01-23 /pmc/articles/PMC3900421/ /pubmed/24465552 http://dx.doi.org/10.1371/journal.pone.0085409 Text en © 2014 Kher et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kher, Swapnil S.
Struckhoff, Amanda P.
Alberts, Arthur S.
Worthylake, Rebecca A
A Novel Role for p115RhoGEF in Regulation of Epithelial Plasticity
title A Novel Role for p115RhoGEF in Regulation of Epithelial Plasticity
title_full A Novel Role for p115RhoGEF in Regulation of Epithelial Plasticity
title_fullStr A Novel Role for p115RhoGEF in Regulation of Epithelial Plasticity
title_full_unstemmed A Novel Role for p115RhoGEF in Regulation of Epithelial Plasticity
title_short A Novel Role for p115RhoGEF in Regulation of Epithelial Plasticity
title_sort novel role for p115rhogef in regulation of epithelial plasticity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900421/
https://www.ncbi.nlm.nih.gov/pubmed/24465552
http://dx.doi.org/10.1371/journal.pone.0085409
work_keys_str_mv AT kherswapnils anovelroleforp115rhogefinregulationofepithelialplasticity
AT struckhoffamandap anovelroleforp115rhogefinregulationofepithelialplasticity
AT albertsarthurs anovelroleforp115rhogefinregulationofepithelialplasticity
AT worthylakerebeccaa anovelroleforp115rhogefinregulationofepithelialplasticity
AT kherswapnils novelroleforp115rhogefinregulationofepithelialplasticity
AT struckhoffamandap novelroleforp115rhogefinregulationofepithelialplasticity
AT albertsarthurs novelroleforp115rhogefinregulationofepithelialplasticity
AT worthylakerebeccaa novelroleforp115rhogefinregulationofepithelialplasticity