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Modelling GTPase dynamics to understand RhoA-driven cancer cell invasion

Metastasis, initially driven by cells migrating and invading through the local environment, leads to most cancer-associated deaths. Cells can use a variety of modes to move in vitro, all of which depend on Rho GTPases at some level. While traditionally it was thought that Rac1 activity drives protru...

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Autores principales: Hetmanski, Joseph H.R., Schwartz, Jean-Marc, Caswell, Patrick T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5134997/
https://www.ncbi.nlm.nih.gov/pubmed/27913679
http://dx.doi.org/10.1042/BST20160184
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author Hetmanski, Joseph H.R.
Schwartz, Jean-Marc
Caswell, Patrick T.
author_facet Hetmanski, Joseph H.R.
Schwartz, Jean-Marc
Caswell, Patrick T.
author_sort Hetmanski, Joseph H.R.
collection PubMed
description Metastasis, initially driven by cells migrating and invading through the local environment, leads to most cancer-associated deaths. Cells can use a variety of modes to move in vitro, all of which depend on Rho GTPases at some level. While traditionally it was thought that Rac1 activity drives protrusive lamellipodia at the leading edge of a polarised cell while RhoA drives rear retraction, more recent work in 3D microenvironments has revealed a much more complicated picture of GTPase dynamics. In particular, RhoA activity can dominate the leading edge polymerisation of actin to form filopodial actin-spike protrusions that drive more invasive cell migration. We recently described a potential mechanism to abrogate this pro-invasive localised leading edge Rac1 to RhoA switch via manipulation of a negative feedback loop that was revealed by adopting a logical modelling approach. Both challenging dogma and taking a formal, mathematical approach to understanding signalling involved in motility may be vital to harnessing harmful cell migration and preventing metastasis in future research.
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spelling pubmed-51349972016-12-16 Modelling GTPase dynamics to understand RhoA-driven cancer cell invasion Hetmanski, Joseph H.R. Schwartz, Jean-Marc Caswell, Patrick T. Biochem Soc Trans Cytoskeleton, Cell Adhesion and Migration Metastasis, initially driven by cells migrating and invading through the local environment, leads to most cancer-associated deaths. Cells can use a variety of modes to move in vitro, all of which depend on Rho GTPases at some level. While traditionally it was thought that Rac1 activity drives protrusive lamellipodia at the leading edge of a polarised cell while RhoA drives rear retraction, more recent work in 3D microenvironments has revealed a much more complicated picture of GTPase dynamics. In particular, RhoA activity can dominate the leading edge polymerisation of actin to form filopodial actin-spike protrusions that drive more invasive cell migration. We recently described a potential mechanism to abrogate this pro-invasive localised leading edge Rac1 to RhoA switch via manipulation of a negative feedback loop that was revealed by adopting a logical modelling approach. Both challenging dogma and taking a formal, mathematical approach to understanding signalling involved in motility may be vital to harnessing harmful cell migration and preventing metastasis in future research. Portland Press Ltd. 2016-12-15 2016-12-02 /pmc/articles/PMC5134997/ /pubmed/27913679 http://dx.doi.org/10.1042/BST20160184 Text en © 2016 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0) .
spellingShingle Cytoskeleton, Cell Adhesion and Migration
Hetmanski, Joseph H.R.
Schwartz, Jean-Marc
Caswell, Patrick T.
Modelling GTPase dynamics to understand RhoA-driven cancer cell invasion
title Modelling GTPase dynamics to understand RhoA-driven cancer cell invasion
title_full Modelling GTPase dynamics to understand RhoA-driven cancer cell invasion
title_fullStr Modelling GTPase dynamics to understand RhoA-driven cancer cell invasion
title_full_unstemmed Modelling GTPase dynamics to understand RhoA-driven cancer cell invasion
title_short Modelling GTPase dynamics to understand RhoA-driven cancer cell invasion
title_sort modelling gtpase dynamics to understand rhoa-driven cancer cell invasion
topic Cytoskeleton, Cell Adhesion and Migration
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5134997/
https://www.ncbi.nlm.nih.gov/pubmed/27913679
http://dx.doi.org/10.1042/BST20160184
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