Abstract
Persistently activated STAT3 contributes to cell survival in many different human cancers. Cancer cell secretion of IL-6 is a frequent basis for persistent STAT3 activation; we show that antibodies against IL-6 or gp-130, the signaling unit of the IL-6 receptor, can abruptly remove persistently activated STAT3 causing prompt disappearance of cysteine proteases of serpin B3/B4 mRNAs, known as squamous cell carcinoma antigens 1 and 2. STAT3 occupies the promoter of serpin B3/B4 before removal and siRNA removal of B3/B4 mRNA caused cell death in HN13 head and neck cancer cells. Thus persistently activated STAT3 is a required part of the continuous activation of B3/B4 genes, which protects tumor cells from dying.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Antibodies / immunology
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Antigens, Neoplasm / genetics*
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Carcinoma, Squamous Cell / metabolism
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Carcinoma, Squamous Cell / pathology*
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Cell Line, Tumor
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Cell Survival / genetics
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Chromatin Immunoprecipitation
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Cytokine Receptor gp130 / analysis
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Cytokine Receptor gp130 / immunology
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Gene Expression Regulation, Neoplastic*
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Humans
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Interleukin-6 / antagonists & inhibitors
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Interleukin-6 / immunology
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Promoter Regions, Genetic
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STAT3 Transcription Factor / metabolism*
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Serpins / genetics*
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Transcriptional Activation*
Substances
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Antibodies
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Antigens, Neoplasm
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IL6ST protein, human
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Interleukin-6
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STAT3 Transcription Factor
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STAT3 protein, human
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Serpins
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squamous cell carcinoma-related antigen
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Cytokine Receptor gp130