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
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.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
Total Visit :2,088,166
Total Download :881,305
Today View :243
Ajou University Medical Information & Media Center 164 Worldcup-ro Yeongtong-gu Suwon 16499 Korea / TEL : 031-219-5312 / FAX : 031-219-5314 Copyright (c) Ajou University Medical Information & Media Center All Rights Reserved. AJOU Open Repository는 국립중앙도서관 OAK 보급사업으로 구축되었습니다.