A STAT3/NF{kappa}B Complex is Necessary for the Expression of Fascin in Metastatic Breast Cancer Cells in Response to IL-6 and TNF-{alpha} [Molecular Bases of Disease]

September 11th, 2014 by Snyder, M., Huang, J., Huang, X.-Y., Zhang, J. J.

IL-6 mediated activation of Stat3 (Signal Transducer and Activator of Transcription 3) 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.
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