Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease

Autores
Larive, Ramon; Moriggi, Giulia; Menacho Márquez, Mauricio Ariel; Cañamero, Marta; de Alava, Enrique; Alarcón, Balbino; Dosil, Mercedes; Bustelo, Xosé R.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
R-Ras2 is a transforming GTPase that shares downstream effectors with Ras subfamily proteins. However, little information exists about the function of this protein in tumorigenesis and its signalling overlap with classical Ras GTPases. Here we show, by combining loss- and gain-of-function studies in breast cancer cells, mammary epithelial cells and mouse models, that endogenous R-Ras2 has a role in both primary breast tumorigenesis and the late metastatic steps of cancer cells in the lung parenchyma. R-Ras2 drives tumorigenesis in a phosphatidylinostiol-3 kinase (PI3K)-dependent and signalling autonomous manner. By contrast, its prometastatic role requires other priming oncogenic signals and the engagement of several downstream elements. R-Ras2 function is required even in cancer cells exhibiting constitutive activation of classical Ras proteins, indicating that these GTPases are not functionally redundant. Our results also suggest that application of long-term R-Ras2 therapies will result in the development of compensatory mechanisms in breast tumours
Fil: Larive, Ramon. Universidad de Salamanca; España. University of Montpellier I and II; Francia
Fil: Moriggi, Giulia. Universidad de Salamanca; España
Fil: Menacho Márquez, Mauricio Ariel. Universidad de Salamanca; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Cañamero, Marta. Centro Nacional de Investigaciones Oncológicas; España
Fil: de Alava, Enrique. Universidad de Salamanca; España. Hospital Universitario Virgen del Rocío. Sevilla; España
Fil: Alarcón, Balbino. Centro de Biología Molecular ‘‘Severo Ochoa’. Madrid; España
Fil: Dosil, Mercedes. Universidad de Salamanca; España
Fil: Bustelo, Xosé R.. Universidad de Salamanca; España
Materia
Ras
R-Ras2
Tc21
Gtpases
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/30099
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/30099
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic diseaseLarive, RamonMoriggi, GiuliaMenacho Márquez, Mauricio ArielCañamero, Martade Alava, EnriqueAlarcón, BalbinoDosil, MercedesBustelo, Xosé R.RasR-Ras2Tc21Gtpaseshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1R-Ras2 is a transforming GTPase that shares downstream effectors with Ras subfamily proteins. However, little information exists about the function of this protein in tumorigenesis and its signalling overlap with classical Ras GTPases. Here we show, by combining loss- and gain-of-function studies in breast cancer cells, mammary epithelial cells and mouse models, that endogenous R-Ras2 has a role in both primary breast tumorigenesis and the late metastatic steps of cancer cells in the lung parenchyma. R-Ras2 drives tumorigenesis in a phosphatidylinostiol-3 kinase (PI3K)-dependent and signalling autonomous manner. By contrast, its prometastatic role requires other priming oncogenic signals and the engagement of several downstream elements. R-Ras2 function is required even in cancer cells exhibiting constitutive activation of classical Ras proteins, indicating that these GTPases are not functionally redundant. Our results also suggest that application of long-term R-Ras2 therapies will result in the development of compensatory mechanisms in breast tumoursFil: Larive, Ramon. Universidad de Salamanca; España. University of Montpellier I and II; FranciaFil: Moriggi, Giulia. Universidad de Salamanca; EspañaFil: Menacho Márquez, Mauricio Ariel. Universidad de Salamanca; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Cañamero, Marta. Centro Nacional de Investigaciones Oncológicas; EspañaFil: de Alava, Enrique. Universidad de Salamanca; España. Hospital Universitario Virgen del Rocío. Sevilla; EspañaFil: Alarcón, Balbino. Centro de Biología Molecular ‘‘Severo Ochoa’. Madrid; EspañaFil: Dosil, Mercedes. Universidad de Salamanca; EspañaFil: Bustelo, Xosé R.. Universidad de Salamanca; EspañaNature Publishing Group2014-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/30099Larive, Ramon; Moriggi, Giulia; Menacho Márquez, Mauricio Ariel; Cañamero, Marta; de Alava, Enrique; et al.; Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease; Nature Publishing Group; Nature Communications; 5; 3881; 5-2014; 1-142041-1723CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/ncomms4881info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/ncomms4881info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:26:10Zoai:ri.conicet.gov.ar:11336/30099instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:26:11.029CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease
title Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease
spellingShingle Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease
Larive, Ramon
Ras
R-Ras2
Tc21
Gtpases
title_short Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease
title_full Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease
title_fullStr Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease
title_full_unstemmed Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease
title_sort Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease
dc.creator.none.fl_str_mv Larive, Ramon
Moriggi, Giulia
Menacho Márquez, Mauricio Ariel
Cañamero, Marta
de Alava, Enrique
Alarcón, Balbino
Dosil, Mercedes
Bustelo, Xosé R.
author Larive, Ramon
author_facet Larive, Ramon
Moriggi, Giulia
Menacho Márquez, Mauricio Ariel
Cañamero, Marta
de Alava, Enrique
Alarcón, Balbino
Dosil, Mercedes
Bustelo, Xosé R.
author_role author
author2 Moriggi, Giulia
Menacho Márquez, Mauricio Ariel
Cañamero, Marta
de Alava, Enrique
Alarcón, Balbino
Dosil, Mercedes
Bustelo, Xosé R.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ras
R-Ras2
Tc21
Gtpases
topic Ras
R-Ras2
Tc21
Gtpases
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv R-Ras2 is a transforming GTPase that shares downstream effectors with Ras subfamily proteins. However, little information exists about the function of this protein in tumorigenesis and its signalling overlap with classical Ras GTPases. Here we show, by combining loss- and gain-of-function studies in breast cancer cells, mammary epithelial cells and mouse models, that endogenous R-Ras2 has a role in both primary breast tumorigenesis and the late metastatic steps of cancer cells in the lung parenchyma. R-Ras2 drives tumorigenesis in a phosphatidylinostiol-3 kinase (PI3K)-dependent and signalling autonomous manner. By contrast, its prometastatic role requires other priming oncogenic signals and the engagement of several downstream elements. R-Ras2 function is required even in cancer cells exhibiting constitutive activation of classical Ras proteins, indicating that these GTPases are not functionally redundant. Our results also suggest that application of long-term R-Ras2 therapies will result in the development of compensatory mechanisms in breast tumours
Fil: Larive, Ramon. Universidad de Salamanca; España. University of Montpellier I and II; Francia
Fil: Moriggi, Giulia. Universidad de Salamanca; España
Fil: Menacho Márquez, Mauricio Ariel. Universidad de Salamanca; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Cañamero, Marta. Centro Nacional de Investigaciones Oncológicas; España
Fil: de Alava, Enrique. Universidad de Salamanca; España. Hospital Universitario Virgen del Rocío. Sevilla; España
Fil: Alarcón, Balbino. Centro de Biología Molecular ‘‘Severo Ochoa’. Madrid; España
Fil: Dosil, Mercedes. Universidad de Salamanca; España
Fil: Bustelo, Xosé R.. Universidad de Salamanca; España
description R-Ras2 is a transforming GTPase that shares downstream effectors with Ras subfamily proteins. However, little information exists about the function of this protein in tumorigenesis and its signalling overlap with classical Ras GTPases. Here we show, by combining loss- and gain-of-function studies in breast cancer cells, mammary epithelial cells and mouse models, that endogenous R-Ras2 has a role in both primary breast tumorigenesis and the late metastatic steps of cancer cells in the lung parenchyma. R-Ras2 drives tumorigenesis in a phosphatidylinostiol-3 kinase (PI3K)-dependent and signalling autonomous manner. By contrast, its prometastatic role requires other priming oncogenic signals and the engagement of several downstream elements. R-Ras2 function is required even in cancer cells exhibiting constitutive activation of classical Ras proteins, indicating that these GTPases are not functionally redundant. Our results also suggest that application of long-term R-Ras2 therapies will result in the development of compensatory mechanisms in breast tumours
publishDate 2014
dc.date.none.fl_str_mv 2014-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/30099
Larive, Ramon; Moriggi, Giulia; Menacho Márquez, Mauricio Ariel; Cañamero, Marta; de Alava, Enrique; et al.; Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease; Nature Publishing Group; Nature Communications; 5; 3881; 5-2014; 1-14
2041-1723
CONICET Digital
CONICET
url http://hdl.handle.net/11336/30099
identifier_str_mv Larive, Ramon; Moriggi, Giulia; Menacho Márquez, Mauricio Ariel; Cañamero, Marta; de Alava, Enrique; et al.; Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease; Nature Publishing Group; Nature Communications; 5; 3881; 5-2014; 1-14
2041-1723
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/ncomms4881
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/ncomms4881
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846082704140926976
score 13.22299

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