Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease
| Autor: | Xosé R. Bustelo, Giulia Moriggi, Marta Cañamero, Mauricio Menacho-Márquez, Mercedes Dosil, Balbino Alarcón, Romain M. Larive, Enrique de Alava |
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| Přispěvatelé: | Asociación Española Contra el Cáncer, Ministerio de Economía y Competitividad (España), Junta de Castilla y León, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM) |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Lung Neoplasms
Carcinogenesis General Physics and Astronomy GTPase medicine.disease_cause Carcinogenesis/*genetics Metastasis purl.org/becyt/ford/1 [https] Mice Ras subfamily Lung Neoplasms/genetics/secondary Neoplasm Metastasis Neoplasm Metastasis/genetics Tumor Multidisciplinary Kinase Adenocarcinoma/*genetics/secondary 3. Good health CIENCIAS NATURALES Y EXACTAS G protein Otras Ciencias Biológicas [SDV.CAN]Life Sciences [q-bio]/Cancer Breast Neoplasms Adenocarcinoma Biology Gtpases General Biochemistry Genetics and Molecular Biology Monomeric GTP-Binding Proteins/genetics Cell Line Ciencias Biológicas Cell Line Tumor medicine Animals Humans Membrane Proteins/genetics purl.org/becyt/ford/1.6 [https] PI3K/AKT/mTOR pathway Monomeric GTP-Binding Proteins Animal Membrane Proteins General Chemistry medicine.disease Tc21 Disease Models Animal Breast Neoplasms/*genetics/pathology Disease Models Immunology Cancer cell Cancer research R-Ras2 Ras |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Digital.CSIC. Repositorio Institucional del CSIC instname Nature Communications Nature Communications, Nature Publishing Group, 2014, 5, pp.3881. ⟨10.1038/ncomms4881⟩ |
| ISSN: | 2041-1723 |
| Popis: | 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. © 2014 Macmillan Publishers Limited. All rights reserved. This work has been primarily supported by a cooperative grant from the Spanish Association Against Cancer (AECC) to both X.R.B. and B.A. Additional funding includes grants from the Castilla-Leon Autonomous Government to X.R.B. (CSI039A12-1) and the Spanish Ministry of Economy and Competitiveness. |
| Databáze: | OpenAIRE |
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