The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis.
The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis.
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DOI：
10.1038/s41467-017-01829-1
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发表时间：
2017-11-21
影响因子：
16.6
通讯作者：
Brancaccio M
中科院分区：
文献类型：
--
作者：
Fusella F;Seclì L;Busso E;Krepelova A;Moiso E;Rocca S;Conti L;Annaratone L;Rubinetto C;Mello-Grand M;Singh V;Chiorino G;Silengo L;Altruda F;Turco E;Morotti A;Oliviero S;Castellano I;Cavallo F;Provero P;Tarone G;Brancaccio M
NF-κB是一种转录因子，参与多种生理和病理细胞过程的调节，包括炎症、细胞存活、增殖和癌细胞转移。NF-κB在包括三阴性乳腺癌在内的几种癌症中经常过度活化。在这里，我们表明，NF-κB在乳腺癌细胞中的激活依赖于CHRDC 1基因产物Morgana的存在，这是一种以前未知的IKK复合物组分，对IκBα底物识别至关重要。Morgana沉默阻断乳腺癌小鼠模型中的转移形成，并且该表型通过IκBα下调而逆转。癌细胞中的高Morgana表达水平减少了肿瘤生长的第一阶段中自然杀伤细胞的募集，并诱导能够吸引原发性肿瘤以及转移前肺中的嗜中性粒细胞的细胞因子的表达，从而促进癌症转移。因此，高Morgana水平与NF-κB靶基因表达和人类患者的不良预后呈正相关。NF-κB调节炎症、细胞存活、增殖和转移，并且通常在三阴性乳腺癌中过度活化。在这里，作者表明Morgana是一种在三阴性乳腺癌中高度表达的蛋白质，它驱动NF-κ B活化以促进转移和中性粒细胞募集。
NF-κB is a transcription factor involved in the regulation of multiple physiological and pathological cellular processes, including inflammation, cell survival, proliferation, and cancer cell metastasis. NF-κB is frequently hyperactivated in several cancers, including triple-negative breast cancer. Here we show that NF-κB activation in breast cancer cells depends on the presence of the CHORDC1 gene product Morgana, a previously unknown component of the IKK complex and essential for IκBα substrate recognition. Morgana silencing blocks metastasis formation in breast cancer mouse models and this phenotype is reverted by IκBα downregulation. High Morgana expression levels in cancer cells decrease recruitment of natural killer cells in the first phases of tumor growth and induce the expression of cytokines able to attract neutrophils in the primary tumor, as well as in the pre-metastatic lungs, fueling cancer metastasis. In accordance, high Morgana levels positively correlate with NF-κB target gene expression and poor prognosis in human patients. NF-κB regulates inflammation, cell survival, proliferation, and metastasis and is often hyperactivated in triple-negative breast cancer. Here the authors show that Morgana, a protein highly expressed in triple-negative breast cancers, drives NF-kB activation to promote metastasis and neutrophil recruitment.
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影响因子：
3.5
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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通讯作者：
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作者：
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通讯作者：
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