PLoS ONE：乳腺癌复发的新鉴定指标

近日，IMIM研究所的研究人员证实乳腺癌细胞中14-3-3蛋白sigma与肿瘤细胞激活NF-kB蛋白复合物的能力有直接联系，NF-kB的激活关系到肿瘤进展。肿瘤中NF-kB的活化情况也被确定为乳腺癌患者复发的最佳指标。研究人员还介绍了一组乳腺癌细胞中以及其他；类型肿瘤细胞中被激活的于肿瘤预后较差相关的基因。

早期研究发现14-3-3蛋白sigma不存在于许多乳腺癌患者体内。现在研究发现这种蛋白质的缺乏并不是这些类型癌症的预后因素之一，虽然14-3-3蛋白sigma 为NF-kB的保持长期保持活化状态，进而促进肿瘤浸润和转移是必须的。

在西方国家，乳腺癌是最常见的妇女患癌类型，其复发和转移是本病的致命结果。参与该项研究的约100名患者体内都缺乏14-3-3 sigma蛋白，或许该蛋白可以作为预后和诊断的一个重要指标。

研究人员表示在以后的研究中将逐步确定能诱导14-3-3蛋白在乳腺肿瘤组织中表达的药物，14-3-3蛋白sigma可能是将来研究治疗靶点中的重要成员。

doi:10.1371/journal.pone.0038347
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Inhibition of Specific NF-κB Activity Contributes to the Tumor Suppressor Function of 14-3-3σ in Breast" Cancer

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, and Lluís Espinosa.

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.