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STAT3 transcriptional factor activated by reactive oxygen species induces IL6 in starvation-induced autophagy of cancer cells.

Yoon, S; Woo, SU; Kang, JH; Kim, K; Kwon, MH; Park, S; Shin, HJ; Gwak, HS; Chwae, YJ
Autophagy, 6(8):1125-1138, 2010
Journal Title
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.
MeSH terms
Amino Acids/deficiency*Amino Acids/pharmacologyAutophagy*/drug effectsBase SequenceCell Proliferation/drug effectsCell Survival/drug effectsCulture Media, Conditioned/pharmacologyEnzyme Activation/drug effectsGene Expression Regulation, Neoplastic/drug effectsGlucose/deficiency*Glucose/pharmacologyHela CellsHumansInterleukin-6/geneticsInterleukin-6/metabolism*Molecular Sequence DataNADPH Oxidase/metabolismNeoplasms/geneticsNeoplasms/pathology*Promoter Regions, Genetic/geneticsProtein Binding/drug effectsReactive Oxygen Species/metabolism*STAT3 Transcription Factor/metabolism*Sirolimus/pharmacologyTranscription, Genetic/drug effects
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
윤, 사라김, 경민권, 명희박, 선신, 호준최, 용준
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