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Inhibition of Specific NF-κB Activity Contributes to the Tumor Suppressor Function of 14-3-3δ in Breast Cancer.
- Source :
- PLoS ONE; May2012, Vol. 7 Issue 5, p1-13, 13p
- Publication Year :
- 2012
-
Abstract
- 14-3-3δ is frequently lost in human breast cancers by genetic deletion or promoter methylation. We have now investigated the involvement of 14-3-3δ in the termination of NF-κB signal in mammary cells and its putative role in cancer relapse and metastasis. Our results show that 14-3-3s regulates nuclear export of p65-NF-κB following chronic TNFa stimulation. Restoration of 14-3-3δ in breast cancer cells reduces migration capacity and metastatic abilities in vivo. By microarray analysis, we have identified a genetic signature that responds to TNFa in a 14-3-3δ-dependent manner and significantly associates with different breast and other types of cancer. By interrogating public databases, we have found that overexpression 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 14-3-3δ 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 [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 79461514
- Full Text :
- https://doi.org/10.1371/journal.pone.0038347