Insights into 14-3-3σ-mediated NF-κB role in breast cancer

14-3-3σ is an adaptor protein that regulates multiple signal transduction pathways. It has been described as a tumour suppressor in breast cancer, where it is often lost or repressed. Anna Bigas and Lluís Espinosa lab, from IMIM, had reported before that 14-3-3 proteins facilitated the nuclear export of p65 and were essential to regulate NF-κB signalling, after stimulation by TNFα.

Last week a paper came out where the role of 14-3-3σ in cancer relapse and metastasis is further investigated, and the kinetics of nuclear p65 export after TNFα stimulation are described. This work has been led by  Anna Bigas and Lluís Espinosa and is the result of a collaboration between reserach groups from the IRB the Hospital del Mar and our group at the UPF. In this publication we contributed in the microarray data interpretation, to describe a genetic signature that responds to TNFα in a 14-3-3σ-dependent manner in MCF7 breast cancer cells. Its over-expression moreover correlates with poor relapse-free survival breast cancer patients. We used IntOGen and Gitools to determine that those genes are associated to breast, intestinal, ovarian and lung cancer. These findings identify a genetic signature that is moreover important for breast cancer prognosis and for future personalized treatments based on NF-κB targeting.

It is always exciting  to blend computational biology analyses and molecular genetics experiments to build a solid story such as this one. I am very glad we had the chance to contribute to it with our knowledge, since I could learn thanks to that.

Inglés-Esteve J, Morales M, Dalmases A, Garcia-Carbonell R, Jené-Sanz A, Lopez-Bigas N, Iglesias M, Ruiz-Herguido C, Rovira A, Rojo F, Albanell J, Gomis RR, Bigas A, Espinosa L. Inhibition of specific NF-kappaB activity contributes to the tumor suppressor function of 14-3-3sigma in breast cancer. PLoS ONE, 7(5): e38347. doi:10.1371/journal.pone.0038347