Inhibition of specific NF-κB activity contributes to the tumor suppressor function of 14-3-3σ in breast cancer.
Inhibition of specific NF-κB activity contributes to the tumor suppressor function of 14-3-3σ in breast cancer.
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DOI：
10.1371/journal.pone.0038347
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Espinosa L
中科院分区：
文献类型：
--
作者：
Inglés-Esteve J;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
14-3-3σ在人类乳腺癌中经常由于基因缺失或启动子甲基化而丢失。我们现在已经研究了14-3-3σ在乳腺细胞中参与NF-κB信号的终止及其在癌症复发和转移中的假定作用。我们的研究结果表明，14-3-3σ调节慢性TNFα刺激后p65-NF-κB的核输出。乳腺癌细胞中14-3-3σ的恢复降低了体内迁移能力和转移能力。通过微阵列分析，我们已经确定了一个基因签名，它以14-3-3σ依赖性方式对TNFα产生反应，并与不同的乳腺癌和其他类型的癌症显著相关。通过查询公共数据库，我们发现这种特征的过度表达与乳腺癌患者的无复发生存率相关。最后，对96例乳腺肿瘤的筛选显示，NF-κB活化与14-3-3σ缺失密切相关，多变量分析显示，NF-κB活化与预后不良显著相关。我们的研究结果确定了一个基因签名，这对乳腺癌预后和未来基于NF-κB靶向的个性化治疗非常重要。
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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影响因子：
12.3
作者：
Gundem G;Lopez-Bigas N
通讯作者：
Lopez-Bigas N
DOI：
10.1073/pnas.0403621101
发表时间：
2004-07-06
影响因子：
11.1
作者：
Biswas, DK;Shi, Q;Iglehart, JD
通讯作者：
Iglehart, JD
影响因子：
4
作者：
Aguilera, Cristina;Fernandez-Majada, Vanessa;Espinosa, Lluis
通讯作者：
Espinosa, Lluis
影响因子：
64.8
作者：
FANTL, WJ;MUSLIN, AJ;WILLIAMS, LT
通讯作者：
WILLIAMS, LT
Ensembl 2009。
影响因子：
14.9
作者：
Hubbard TJ;Aken BL;Ayling S;Ballester B;Beal K;Bragin E;Brent S;Chen Y;Clapham P;Clarke L;Coates G;Fairley S;Fitzgerald S;Fernandez-Banet J;Gordon L;Graf S;Haider S;Hammond M;Holland R;Howe K;Jenkinson A;Johnson N;Kahari A;Keefe D;Keenan S;Kinsella R;Kokocinski F;Kulesha E;Lawson D;Longden I;Megy K;Meidl P;Overduin B;Parker A;Pritchard B;Rios D;Schuster M;Slater G;Smedley D;Spooner W;Spudich G;Trevanion S;Vilella A;Vogel J;White S;Wilder S;Zadissa A;Birney E;Cunningham F;Curwen V;Durbin R;Fernandez-Suarez XM;Herrero J;Kasprzyk A;Proctor G;Smith J;Searle S;Flicek P
通讯作者：
Flicek P