Inglés Esteve, JuliaMorales, MònicaDalmases Massegú, Alba, 1982-Garcia Carbonell, RicardJené i Sanz, Alba, 1984-López Bigas, NúriaIglesias Coma, MarRuiz Herguido, CristinaRovira Guerín, AnaRojo, FedericoAlbanell Mestres, JoanGomis, Roger R.Bigas Salvans, AnnaEspinosa Blay, Lluís2015-05-082015-05-082012Ingles-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.00383471932-6203http://hdl.handle.net/10230/2354014-3-3σ 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.application/pdfeng© 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 creditedProteïnes de la sangMama -- Càncer -- Aspectes genèticsAntioncogensinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1371/journal.pone.0038347info:eu-repo/semantics/openAccess