Inhibition of specific NF-KB activity contributes to the tumor suppressor function of 14-3-3omega in breast cancer
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- dc.contributor.author Inglés Esteve, Juliaca
- dc.contributor.author Morales, Mònicaca
- dc.contributor.author Dalmases Massegú, Alba, 1982-ca
- dc.contributor.author Garcia Carbonell, Ricardca
- dc.contributor.author Jené i Sanz, Alba, 1984-ca
- dc.contributor.author López Bigas, Núriaca
- dc.contributor.author Iglesias Coma, Marca
- dc.contributor.author Ruiz Herguido, Cristinaca
- dc.contributor.author Rovira Guerín, Anaca
- dc.contributor.author Rojo, Federicoca
- dc.contributor.author Albanell Mestres, Joanca
- dc.contributor.author Gomis, Roger R.ca
- dc.contributor.author Bigas Salvans, Annaca
- dc.contributor.author Espinosa Blay, Lluísca
- dc.date.accessioned 2015-05-08T07:19:28Z
- dc.date.available 2015-05-08T07:19:28Z
- dc.date.issued 2012ca
- dc.description.abstract 14-3-3σ is frequently lost in human breast cancers by genetic deletion or promoter methylation. We have now investigated the involvement of 14-3-3σ in the termination of NF-κB signal in mammary cells and its putative role in cancer relapse and metastasis. Our results show that 14-3-3σ regulates nuclear export of p65-NF-κB following chronic TNFα stimulation. Restoration of 14-3-3σ in breast cancer cells reduces migration capacity and metastatic abilities in vivo. By microarray analysis, we have identified a genetic signature that responds to TNFα in a 14-3-3σ-dependent manner and significantly associates with different breast and other types of cancer. By interrogating public databases, we have found that over-expression of this signature correlates with poor relapse-free survival in breast cancer patients. Finally, screening of 96 human breast tumors showed that NF-κB activation strictly correlates with the absence of 14-3-3σ and it is significantly associated with worse prognosis in the multivariate analysis. Our findings identify a genetic signature that is important for breast cancer prognosis and for future personalized treatments based on NF-κB targeting.en
- dc.description.sponsorship This work was funded by ISCIII/FEDER-Subdirección General de Evaluación y Fomento de la Investigación (PI07/0778, PI10/01128, PS09/1296 and PS09/01285), AGAUR (2009SGR23 and 2009SGR321) and Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+I), iniciativa Ingenio 2010, Programa Consolider and Instituto de Salud Carlos III (ISCIII)/FEDER (RD06/0020/0098 and RD06/0020/0109). Financial support was provided to RRG by BBVA foundation and Asociación Española Contra el Cáncer. NLB acknowledges funding from the Spanish Ministry of Science and Technology (SAF2009-06954). AJ-S was funded by Science and Education Spanish Ministry (MEC) FPI predoctoral fellowship (BES-2008-001850). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscripten
- dc.format.mimetype application/pdfca
- dc.identifier.citation Ingles-Esteve J, Morales M, Dalmases A, Garcia-Carbonell R, Jene-Sanz A, López-Bigas N et al. Inhibition of specific NF-KB activity contributes to the tumor suppressor function of 14-3-3omega in breast cancer. PLoS ONE. 2012;7(5):e38347. DOI: 10.1371/journal.pone.0038347ca
- dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0038347
- dc.identifier.issn 1932-6203ca
- dc.identifier.uri http://hdl.handle.net/10230/23540
- dc.language.iso engca
- dc.publisher Public Library of Science (PLoS)ca
- dc.relation.ispartof PLoS ONE. 2012;7(5):e38347
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2009-06954
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BES2008-001850
- dc.rights © 2012 Inglés-Esteve et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are crediteden
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.subject.other Proteïnes de la sangca
- dc.subject.other Mama -- Càncer -- Aspectes genèticsca
- dc.subject.other Antioncogensca
- dc.title Inhibition of specific NF-KB activity contributes to the tumor suppressor function of 14-3-3omega in breast canceren
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca