Stimulation of cortical myosin phosphorylation by p114RhoGEF drives cell migration and tumor cell invasion.

Actinomyosin activity is an important driver of cell locomotion and has been shown to promote collective cell migration of epithelial sheets as well as single cell migration and tumor cell invasion. However, the molecular mechanisms underlying activation of cortical myosin to stimulate single cell m...

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Autores principales:	Stephen J Terry, Ahmed Elbediwy, Ceniz Zihni, Andrew R Harris, Maryse Bailly, Guillaume T Charras, Maria S Balda, Karl Matter
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1ab7cf95323a412fa97309259fa7759c
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spelling	oai:doaj.org-article:1ab7cf95323a412fa97309259fa7759c2021-11-18T08:08:14ZStimulation of cortical myosin phosphorylation by p114RhoGEF drives cell migration and tumor cell invasion.1932-620310.1371/journal.pone.0050188https://doaj.org/article/1ab7cf95323a412fa97309259fa7759c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23185572/?tool=EBIhttps://doaj.org/toc/1932-6203Actinomyosin activity is an important driver of cell locomotion and has been shown to promote collective cell migration of epithelial sheets as well as single cell migration and tumor cell invasion. However, the molecular mechanisms underlying activation of cortical myosin to stimulate single cell movement, and the relationship between the mechanisms that drive single cell locomotion and those that mediate collective cell migration of epithelial sheets are incompletely understood. Here, we demonstrate that p114RhoGEF, an activator of RhoA that associates with non-muscle myosin IIA, regulates collective cell migration of epithelial sheets and tumor cell invasion. Depletion of p114RhoGEF resulted in specific spatial inhibition of myosin activation at cell-cell contacts in migrating epithelial sheets and the cortex of migrating single cells, but only affected double and not single phosphorylation of myosin light chain. In agreement, overall elasticity and contractility of the cells, processes that rely on persistent and more constant forces, were not affected, suggesting that p114RhoGEF mediates process-specific myosin activation. Locomotion was p114RhoGEF-dependent on Matrigel, which favors more roundish cells and amoeboid-like actinomyosin-driven movement, but not on fibronectin, which stimulates flatter cells and lamellipodia-driven, mesenchymal-like migration. Accordingly, depletion of p114RhoGEF led to reduced RhoA, but increased Rac activity. Invasion of 3D matrices was p114RhoGEF-dependent under conditions that do not require metalloproteinase activity, supporting a role of p114RhoGEF in myosin-dependent, amoeboid-like locomotion. Our data demonstrate that p114RhoGEF drives cortical myosin activation by stimulating myosin light chain double phosphorylation and, thereby, collective cell migration of epithelial sheets and amoeboid-like motility of tumor cells.Stephen J TerryAhmed ElbediwyCeniz ZihniAndrew R HarrisMaryse BaillyGuillaume T CharrasMaria S BaldaKarl MatterPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e50188 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stephen J Terry Ahmed Elbediwy Ceniz Zihni Andrew R Harris Maryse Bailly Guillaume T Charras Maria S Balda Karl Matter Stimulation of cortical myosin phosphorylation by p114RhoGEF drives cell migration and tumor cell invasion.
description	Actinomyosin activity is an important driver of cell locomotion and has been shown to promote collective cell migration of epithelial sheets as well as single cell migration and tumor cell invasion. However, the molecular mechanisms underlying activation of cortical myosin to stimulate single cell movement, and the relationship between the mechanisms that drive single cell locomotion and those that mediate collective cell migration of epithelial sheets are incompletely understood. Here, we demonstrate that p114RhoGEF, an activator of RhoA that associates with non-muscle myosin IIA, regulates collective cell migration of epithelial sheets and tumor cell invasion. Depletion of p114RhoGEF resulted in specific spatial inhibition of myosin activation at cell-cell contacts in migrating epithelial sheets and the cortex of migrating single cells, but only affected double and not single phosphorylation of myosin light chain. In agreement, overall elasticity and contractility of the cells, processes that rely on persistent and more constant forces, were not affected, suggesting that p114RhoGEF mediates process-specific myosin activation. Locomotion was p114RhoGEF-dependent on Matrigel, which favors more roundish cells and amoeboid-like actinomyosin-driven movement, but not on fibronectin, which stimulates flatter cells and lamellipodia-driven, mesenchymal-like migration. Accordingly, depletion of p114RhoGEF led to reduced RhoA, but increased Rac activity. Invasion of 3D matrices was p114RhoGEF-dependent under conditions that do not require metalloproteinase activity, supporting a role of p114RhoGEF in myosin-dependent, amoeboid-like locomotion. Our data demonstrate that p114RhoGEF drives cortical myosin activation by stimulating myosin light chain double phosphorylation and, thereby, collective cell migration of epithelial sheets and amoeboid-like motility of tumor cells.
format	article
author	Stephen J Terry Ahmed Elbediwy Ceniz Zihni Andrew R Harris Maryse Bailly Guillaume T Charras Maria S Balda Karl Matter
author_facet	Stephen J Terry Ahmed Elbediwy Ceniz Zihni Andrew R Harris Maryse Bailly Guillaume T Charras Maria S Balda Karl Matter
author_sort	Stephen J Terry
title	Stimulation of cortical myosin phosphorylation by p114RhoGEF drives cell migration and tumor cell invasion.
title_short	Stimulation of cortical myosin phosphorylation by p114RhoGEF drives cell migration and tumor cell invasion.
title_full	Stimulation of cortical myosin phosphorylation by p114RhoGEF drives cell migration and tumor cell invasion.
title_fullStr	Stimulation of cortical myosin phosphorylation by p114RhoGEF drives cell migration and tumor cell invasion.
title_full_unstemmed	Stimulation of cortical myosin phosphorylation by p114RhoGEF drives cell migration and tumor cell invasion.
title_sort	stimulation of cortical myosin phosphorylation by p114rhogef drives cell migration and tumor cell invasion.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/1ab7cf95323a412fa97309259fa7759c
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Stimulation of cortical myosin phosphorylation by p114RhoGEF drives cell migration and tumor cell invasion.

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