| STAT3 transcriptional factor activated by reactive oxygen species induces IL6 in starvation-induced autophagy of cancer cells. | |
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MedLine Citation:
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PMID: 20930550 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Autophagy is one of the survival processes of cancer cells, especially in stressful conditions such as starvation, hypoxia and chemotherapeutic agents. However, its roles in tumor survival have not yet been fully elucidated. Here, we found for the first time that JAK2/STAT3 was activated in HeLa cells when they were starved or treated with rapamycin. STAT3 activation was associated with autophagic processes, because it was completely inhibited by 3-methyladenine, partially inhibited by knockdown of molecules associated with autophagic processes and blocked by antioxidants, DPI, a Nox inhibitor and knockdown of p22 phox, indicating that ROS generated by Nox that was activated during autophagic processes activated JAK2/STAT3 pathway. Activated STAT3 directly bound to IL6 promoter and increased IL6 mRNA and protein secretion. Finally, the conditioned media, which included IL6, from starved HeLa cells promoted cancer cell survival in both normal and starved conditions, confirmed by clonogenic, proliferation and cell death assays. These data together indicate that the autophagic process in cancer cells can contribute to their survival by JAk2/STAT3 activation and subsequent secretion of growth factors. |
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Authors:
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Sarah Yoon; Sang Uk Woo; Jung Hee Kang; Kyongmin Kim; Myung-Hee Kwon; Sun Park; Ho-Joon Shin; Ho-Shin Gwak; Yong-Joon Chwae |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-16 |
Journal Detail:
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Title: Autophagy Volume: 6 ISSN: 1554-8635 ISO Abbreviation: Autophagy Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-16 Completed Date: 2011-03-02 Revised Date: 2011-06-30 |
Medline Journal Info:
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Nlm Unique ID: 101265188 Medline TA: Autophagy Country: United States |
Other Details:
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Languages: eng Pagination: 1125-38 Citation Subset: IM |
Affiliation:
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Department of Microbiology, Ajou University School of Medicine, Suwon, Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids
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deficiency*,
pharmacology Autophagy* / drug effects Base Sequence Cell Proliferation / drug effects Cell Survival / drug effects Culture Media, Conditioned / pharmacology Enzyme Activation / drug effects Gene Expression Regulation, Neoplastic / drug effects Glucose / deficiency*, pharmacology Hela Cells Humans Interleukin-6 / genetics, metabolism* Molecular Sequence Data NADPH Oxidase / metabolism Neoplasms / genetics, pathology* Promoter Regions, Genetic / genetics Protein Binding / drug effects Reactive Oxygen Species / metabolism* STAT3 Transcription Factor / metabolism* Sirolimus / pharmacology Transcription, Genetic / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Culture Media, Conditioned; 0/Interleukin-6; 0/Reactive Oxygen Species; 0/STAT3 Transcription Factor; 50-99-7/Glucose; 53123-88-9/Sirolimus; EC 1.6.3.1/NADPH Oxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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