信号转导和转录激活因子3·核因子κB（Stat3·NFκB）复合物对于转移性乳腺癌细胞中丝状肌动蛋白在白细胞介素（IL）-6和肿瘤坏死因子（TNF）-α刺激下的表达是必需的。
A signal transducer and activator of transcription 3·Nuclear Factor κB (Stat3·NFκB) complex is necessary for the expression of fascin in metastatic breast cancer cells in response to interleukin (IL)-6 and tumor necrosis factor (TNF)-α.
作者信息
Snyder Marylynn, Huang Jianyun, Huang Xin-Yun, Zhang J Jillian
机构信息
From the Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, New York 10065.
From the Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, New York 10065
出版信息
J Biol Chem. 2014 Oct 24;289(43):30082-9. doi: 10.1074/jbc.M114.591719. Epub 2014 Sep 11.
IL-6 mediated activation of Stat3 is a major signaling pathway in the process of breast cancer metastasis. One important mechanism by which the IL-6/Stat3 pathway promotes metastasis is through transcriptional regulation of the actin-bundling protein fascin. In this study, we further analyzed the transcriptional regulation of the fascin gene promoter. We show that in addition to IL-6, TNF-α increases Stat3 and NFκB binding to the fascin promoter to induce its expression. We also show that NFκB is required for Stat3 recruitment to the fascin promoter in response to IL-6. Furthermore, Stat3 and NFκB form a protein complex in response to cytokine stimulation. Finally, we demonstrate that an overlapping STAT/NFκB site in a highly conserved 160-bp region of the fascin promoter is sufficient and necessary to induce transcription in response to IL-6 and TNF-α.
白细胞介素-6（IL-6）介导的信号转导及转录激活因子3（Stat3）的激活是乳腺癌转移过程中的一条主要信号通路。IL-6/Stat3通路促进转移的一个重要机制是通过对肌动蛋白成束蛋白丝聚蛋白的转录调控。在本研究中，我们进一步分析了丝聚蛋白基因启动子的转录调控。我们发现，除了IL-6外，肿瘤坏死因子-α（TNF-α）可增加Stat3和核因子κB（NFκB）与丝聚蛋白启动子的结合，从而诱导其表达。我们还发现，NFκB是Stat3响应IL-6募集到丝聚蛋白启动子所必需的。此外，Stat3和NFκB在细胞因子刺激下形成蛋白复合物。最后，我们证明，丝聚蛋白启动子高度保守的160个碱基对区域中一个重叠的信号转导及转录激活因子/核因子κB（STAT/NFκB）位点对于响应IL-6和TNF-α诱导转录是充分且必要的。
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