Inhibition of specific NF-κB activity contributes to the tumor suppressor function of 14-3-3σ in breast cancer.
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 nucl...
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2012
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oai:doaj.org-article:944020d04a674d06a7a2745816d679242021-11-18T07:16:46ZInhibition of specific NF-κB activity contributes to the tumor suppressor function of 14-3-3σ in breast cancer.1932-620310.1371/journal.pone.0038347https://doaj.org/article/944020d04a674d06a7a2745816d679242012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22675457/pdf/?tool=EBIhttps://doaj.org/toc/1932-620314-3-3σ 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.Julia Inglés-EsteveMònica MoralesAlba DalmasesRicard Garcia-CarbonellAlba Jené-SanzNúria López-BigasMar IglesiasCristina Ruiz-HerguidoAna RoviraFederico RojoJoan AlbanellRoger R GomisAnna BigasLluís EspinosaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e38347 (2012) |
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DOAJ |
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Medicine R Science Q Julia Inglés-Esteve Mònica Morales Alba Dalmases Ricard Garcia-Carbonell Alba Jené-Sanz Núria López-Bigas Mar Iglesias Cristina Ruiz-Herguido Ana Rovira Federico Rojo Joan Albanell Roger R Gomis Anna Bigas Lluís Espinosa Inhibition of specific NF-κB activity contributes to the tumor suppressor function of 14-3-3σ in breast cancer. |
| description |
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. |
| format |
article |
| author |
Julia Inglés-Esteve Mònica Morales Alba Dalmases Ricard Garcia-Carbonell Alba Jené-Sanz Núria López-Bigas Mar Iglesias Cristina Ruiz-Herguido Ana Rovira Federico Rojo Joan Albanell Roger R Gomis Anna Bigas Lluís Espinosa |
| author_facet |
Julia Inglés-Esteve Mònica Morales Alba Dalmases Ricard Garcia-Carbonell Alba Jené-Sanz Núria López-Bigas Mar Iglesias Cristina Ruiz-Herguido Ana Rovira Federico Rojo Joan Albanell Roger R Gomis Anna Bigas Lluís Espinosa |
| author_sort |
Julia Inglés-Esteve |
| title |
Inhibition of specific NF-κB activity contributes to the tumor suppressor function of 14-3-3σ in breast cancer. |
| title_short |
Inhibition of specific NF-κB activity contributes to the tumor suppressor function of 14-3-3σ in breast cancer. |
| title_full |
Inhibition of specific NF-κB activity contributes to the tumor suppressor function of 14-3-3σ in breast cancer. |
| title_fullStr |
Inhibition of specific NF-κB activity contributes to the tumor suppressor function of 14-3-3σ in breast cancer. |
| title_full_unstemmed |
Inhibition of specific NF-κB activity contributes to the tumor suppressor function of 14-3-3σ in breast cancer. |
| title_sort |
inhibition of specific nf-κb activity contributes to the tumor suppressor function of 14-3-3σ in breast cancer. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/944020d04a674d06a7a2745816d67924 |
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