Inhibition of specific NF-κB activity contributes to the tumor suppressor function of 14-3-3σ in breast cancer. - Literature - Data resources

22675457

Inhibition of specific NF-κB activity contributes to the tumor suppressor function of 14-3-3σ in breast cancer.

PLoS One, 2012;7(5):e38347.

Inglés-Esteve J^[1], Morales M, Dalmases A, Garcia-Carbonell R, Jené-Sanz A, López-Bigas N, Iglesias M, Ruiz-Herguido C, Rovira A, Rojo F, Albanell J, Gomis RR, Bigas A, Espinosa L

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PMID: 22675457DOI: 10.1371/journal.pone.0038347

Impact factor: 3.752

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.

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