Activated G(alpha)13 impairs cell invasiveness throught p190RhoGAP-mediated inhibition of RhoA activity

10 páginas, 6 figuras -- PAGS nros. 8221-8230

Detalles Bibliográficos
Autores: Bartolomé, Rubén Álvaro, Wright, Natalia, Molina-Ortiz, Isabel, Sánchez-Luque, Francisco J., Teixidó, Joaquín
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2008
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/56374
Acceso en línea:http://hdl.handle.net/10261/56374
Access Level:acceso abierto
Palabra clave:Chemokines
Melanoma
Invasion
RhoGTPases
Metastasis
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spelling Activated G(alpha)13 impairs cell invasiveness throught p190RhoGAP-mediated inhibition of RhoA activityBartolomé, Rubén ÁlvaroWright, NataliaMolina-Ortiz, IsabelSánchez-Luque, Francisco J.Teixidó, JoaquínChemokinesMelanomaInvasionRhoGTPasesMetastasis10 páginas, 6 figuras -- PAGS nros. 8221-8230The GTPase RhoA is a downstream target of heterotrimeric G(13) proteins and plays key roles in cell migration and invasion. Here, we show that expression in human melanoma cells of a constitutively active, GTPase-deficient Galpha(13) form (G(alpha)(13)QL) or lysophosphatidylcholine (LPC)-promoted signaling through G(alpha)(13)-coupled receptors led to a blockade of chemokine-stimulated RhoA activation and cell invasion that was rescued by active RhoA. Melanoma cells expressing G(alpha)(13)QL or cells stimulated with LPC displayed an increase in p190RhoGAP activation, and defects in RhoA activation and invasion were recovered by knocking down p190RhoGAP expression, thus identifying this GTPase-activating protein (GAP) protein as a downstream G(alpha)(13) target that is responsible for these inhibitory responses. In addition, defective stress fiber assembly and reduced migration speed underlay inefficient invasion of G(alpha)(13)QL melanoma cells. Importantly, G(alpha)(13)QL expression in melanoma cells led to impairment in lung metastasis associated with prolonged survival in SCID mice. The data indicate that G(alpha)(13)-dependent downstream effects on RhoA activation and invasion tightly depend on cell type-specific GAP activities and that G(alpha)(13)-p190RhoGAP signaling might represent a potential target for intervention in melanoma metastasisMinisterio de Educación y Ciencia grant SAF2005-02119 (J. Teixidó), Fundación de Investigación Médica Mutua Madrileña grants (J. Teixidó), and Fundación de Investigación Científica de la Asociación Española contra el Cáncer grants (R.A. Bartolomé). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this factPeer reviewedAmerican Association for Cancer ResearchConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201220122008info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttp://hdl.handle.net/10261/56374reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1158/0008-5472.CAN-08-0561Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/563742026-05-22T06:33:51Z
dc.title.none.fl_str_mv Activated G(alpha)13 impairs cell invasiveness throught p190RhoGAP-mediated inhibition of RhoA activity
title Activated G(alpha)13 impairs cell invasiveness throught p190RhoGAP-mediated inhibition of RhoA activity
spellingShingle Activated G(alpha)13 impairs cell invasiveness throught p190RhoGAP-mediated inhibition of RhoA activity
Bartolomé, Rubén Álvaro
Chemokines
Melanoma
Invasion
RhoGTPases
Metastasis
title_short Activated G(alpha)13 impairs cell invasiveness throught p190RhoGAP-mediated inhibition of RhoA activity
title_full Activated G(alpha)13 impairs cell invasiveness throught p190RhoGAP-mediated inhibition of RhoA activity
title_fullStr Activated G(alpha)13 impairs cell invasiveness throught p190RhoGAP-mediated inhibition of RhoA activity
title_full_unstemmed Activated G(alpha)13 impairs cell invasiveness throught p190RhoGAP-mediated inhibition of RhoA activity
title_sort Activated G(alpha)13 impairs cell invasiveness throught p190RhoGAP-mediated inhibition of RhoA activity
dc.creator.none.fl_str_mv Bartolomé, Rubén Álvaro
Wright, Natalia
Molina-Ortiz, Isabel
Sánchez-Luque, Francisco J.
Teixidó, Joaquín
author Bartolomé, Rubén Álvaro
author_facet Bartolomé, Rubén Álvaro
Wright, Natalia
Molina-Ortiz, Isabel
Sánchez-Luque, Francisco J.
Teixidó, Joaquín
author_role author
author2 Wright, Natalia
Molina-Ortiz, Isabel
Sánchez-Luque, Francisco J.
Teixidó, Joaquín
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Chemokines
Melanoma
Invasion
RhoGTPases
Metastasis
topic Chemokines
Melanoma
Invasion
RhoGTPases
Metastasis
description 10 páginas, 6 figuras -- PAGS nros. 8221-8230
publishDate 2008
dc.date.none.fl_str_mv 2008
2012
2012
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/56374
url http://hdl.handle.net/10261/56374
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1158/0008-5472.CAN-08-0561
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Association for Cancer Research
publisher.none.fl_str_mv American Association for Cancer Research
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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