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J Biol Chem. 2014 Oct 24;289(43):30082-9. doi: 10.1074/jbc.M114.591719. Epub 2014 Sep 11.

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.

Author information

1
From the Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, New York 10065.
2
From the Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, New York 10065 jjz2002@med.cornell.edu.

Abstract

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.

KEYWORDS:

Breast Cancer; Fascin, NF KappaB; Stat3; Transcription Regulation; Tumor Metastasis; Tumor Necrosis Factor (TNF)

PMID:
25213863
PMCID:
PMC4208015
DOI:
10.1074/jbc.M114.591719
[Indexed for MEDLINE]
Free PMC Article

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