title: 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.
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.
authors.affiliation: From the Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, New York 10065.
authors.forename: Marylynn
authors.initials: M
authors.lastname: Snyder
authors.affiliation: From the Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, New York 10065.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Huang
authors.affiliation: From the Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, New York 10065.
authors.forename: Xin-Yun
authors.initials: XY
authors.lastname: Huang
authors.affiliation: From the Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, New York 10065 jjz2002@med.cornell.edu.
authors.forename: J Jillian
authors.initials: JJ
authors.lastname: Zhang
mesh_terms: D020029:Base Pairing / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D017124:Conserved Sequence; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008156:Luciferases / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D015850:Interleukin-6; D008840:Microfilament Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C020324:fascin; D008156:Luciferases
keywords: Breast Cancer; Fascin, NF KappaB; Stat3; Transcription Regulation; Tumor Metastasis; Tumor Necrosis Factor (TNF)