Serpin B3/B4, activated by STAT3, promote survival of squamous carcinoma cells.
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.
Ahmed
Simi T
ST
Laboratory of Molecular Cell Biology, The Rockefeller University, New York, NY 10065, USA.
Darnell
James E
JE
D000906:Antibodies / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D050822:Cytokine Receptor gp130 / Q000032:analysis / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D011401:Promoter Regions, Genetic; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015843:Serpins / Q000235:genetics*; D015533:Transcriptional Activation; D000093242:Interleukin-6 Inhibitors
D000906:Antibodies; D000951:Antigens, Neoplasm; D050822:Cytokine Receptor gp130; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D015843:Serpins; D000093242:Interleukin-6 Inhibitors; C494199:IL6ST protein, human; C494086:STAT3 protein, human; C051072:squamous cell carcinoma-related antigen