Cited by 163Autophagy in Disease and TherapyCytokine Signaling Pathways and InteractionsTGF-β signaling in diseases

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

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Yoon, Sarah, Woo, Sang Uk, Kang, Jung Hee, Kim, Kyongmin, Kwon, Myung-Hee, Park, Sun, Shin, Ho-Joon, Gwak, Ho-Shin, Chwae, Yong-Joon·2010·Autophagy

DOI 10.4161/auto.6.8.13547

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Abstract

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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Additional file 1 of Primary high-grade serous ovarian cancer cells are sensitive to senescence induced by carboplatin and paclitaxel in vitro
Uruski, P., Sepetowska, A., Konieczna, C., Pakuła, M., Wyrwa, M., Tussupkaliyev, A., Tykarski, A., Mikuła‐Pietrasik, J., & Książek, K. (2021) · Figshare · doi:10.6084/m9.figshare.16851490
Additional file 3 of CYB561D2 up-regulation activates STAT3 to induce immunosuppression and aggression in gliomas
陶帮宝, Shi, J., Shuai, S., Zhou, H., Zhang, H., Li, B., Wang, X., Li, G., He, H., & Zhong, J. (2021) · Figshare · doi:10.6084/m9.figshare.15139688
Additional file 1 of CYB561D2 up-regulation activates STAT3 to induce immunosuppression and aggression in gliomas
陶帮宝, Shi, J., Shuai, S., Zhou, H., Zhang, H., Li, B., Wang, X., Li, G., He, H., & Zhong, J. (2021) · Figshare · doi:10.6084/m9.figshare.15139679
Additional file 2 of CYB561D2 up-regulation activates STAT3 to induce immunosuppression and aggression in gliomas
陶帮宝, Shi, J., Shuai, S., Zhou, H., Zhang, H., Li, B., Wang, X., Li, G., He, H., & Zhong, J. (2021) · Figshare · doi:10.6084/m9.figshare.15139685
Autophagy in cancer-associated fibroblasts: its role in gastrointestinal cancers
Kuppala, V., Chintapudi, H., Gopalaiah, K., Nagaraju, G. P., & El‐Rayes, B. F. (2026) · Molecular Cancer · doi:10.1186/s12943-026-02626-5
“STAT3 promotes transcription of autophagy-related genes [131].”
Fonctions oncogéniques de STAT5 : rôle dans la régulation du métabolisme oxydatif
Bourgeais, J. (2015) · theses.fr (ABES) · doi:10.70675/642a7bdcz3eb5z47fcza4fez4dd048c937e2
Spatially controlled tenascin-C accumulation contributes to inflammatory disease persistence in giant cell aortitis
Shi, H., Ying, T. A. N. G., Li, J., Gewurz‐Singer, O., Yang, B., & Mizrak, D. (2026) · JCI Insight · doi:10.1172/jci.insight.200255
“…inhibiting the myocardin–serum response factor transcriptional complex (54) and is a transcriptional regulator of IL6 expression in a positive feedback loop (55, 56), as also evidenced by the STAT3 binding peaks (ENCODE Project Consortium) (57) in the IL6 promoter region (Supplemental Figure 3H).”
Rôle du microenvironnement adipeux inflammatoire dans la progression du cancer mammaire canalaire in situ : optimisation d'un modèle 3D de tumoroïde bicellulaire bifluorescent
Habanjar, O. (2023) · theses.fr (ABES) · doi:10.70675/89bce76az0d1ez4875zb52ez1bc825a3d113
Dual-responsive peptide nanoplatform for improved lung cancer therapy via the synergistic suppression of autophagy and drug efflux
Liu, Z., Li, H., Gao, W., Wang, W., Li, C., Huang, H., Liu, J., Li, J. S., Jia, H., Ma, C., et al. (2026) · Materials Today Bio · doi:10.1016/j.mtbio.2026.103232
“Among these, the induced activation of autophagy — a highly conserved intracellular degradation process — is considered one of the key mechanisms through which cancer cells maintain survival under chemotherapy stress [9,10].”
Multi‐Target Mechanisms of Citrus Essential Oils in Cosmetics: Chemical Profiling, Bioactivity Assessment, and Network Pharmacology Insights
Kou, X., Yan, C. H. E. N., 山永芳, Qinfei, K. E., Chen, F., Wang, H., & Meng, Q. (2026) · Flavour and Fragrance Journal · doi:10.1002/ffj.70130
Role of Inflammatory Cytokines Interleukin-1β and Interleukin-6 in Carcinogenesis, with Particular Emphasis on Gastroenteropancreatic Neuroendocrine Neoplasms
Ryguła, I., Rosiek, V., & Kos‐Kudła, B. (2026) · Cancers · doi:10.3390/cancers18142257
Chronic stress regulates endometrial autophagy through IL-6/JAK2/BECN1 signaling pathway
曹欣欣, Wang, Y., Gao, D., Chen, J., Wang, X., Liu, X., & Lei, M. (2026) · Biology of Reproduction · doi:10.1093/biolre/ioag173
STAT3-mediated suppression of the pre-induction silencer Ets-2 in activated T helper cells
Theodoraki, V., Lazaris, C., Mouzaki, Α., & Georgakopoulos, T. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-12699-6
“The β-actin promoter (TATA region) served as a negative control, and the IL-6 promoter GAS element, where STAT3 binding is well established [ 40], served as a positive control.”
Nrf2 and STAT3 Pathways in Protecting Against Methylmercury-Induced Oxidative Stress in Hypothalamic Neuronal GT1-7 Cells
Ferrer, B., Tinkov, A. A., Santamaria, A., Rocha, J. B., Skalny, A. V., Bowman, A. B., & Aschner, M. (2026) · Neurochemical Research · doi:10.1007/s11064-026-04898-1
“While some studies have reported that oxidative stress impairs STAT3 transcriptional activity [19–21], others have observed increased STAT3 phosphorylation and nuclear translocation following exposure to various oxidative stimuli [22–24].”
Influential

Authors: Yoon, S., Woo, S. U., Kang, J. H., Kim, K., Kwon, M.-H., Park, S., Shin, H.-J., Gwak, H.-S., & Chwae, Y.-J.
Affiliations: Ajou University (KR)
National Cancer Center (KR)
ORCID: Yoon, Sarah
Kim, Kyongmin
Kwon, Myung-Hee
Park, Sun
Shin, Ho-Joon
Gwak, Ho-Shin
Chwae, Yong-Joon
Venue: Autophagy
Publisher: Informa UK Limited
Published: 2010-11-16
Volume: 6
Issue: 8
Pages: 1125-1138
ISSN: 1554-8627 (ISSN-L)
1554-8635
DOI: 10.4161/auto.6.8.13547
OpenAlex: W1991688383
Cited by: 163
References: 0
Citations by year: 2026: 9 · 2025: 4 · 2024: 6 · 2023: 8 · 2022: 12 · 2021: 18 · 2020: 11 · 2019: 12 · 2018: 10 · 2017: 12 · 2016: 6 · 2015: 13 · 2014: 15 · 2013: 17 · 2012: 4
FWCI: 6.30
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Autophagy (publishedVersion)
PubMed (publishedVersion)
AJOU Open Repository (Ajou University) (submittedVersion)
Funders: National Research Foundation
Hallym University
National Research Foundation of Korea
Korea Science and Engineering Foundation (R13-2003-019)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords: STAT3, JAK2/STAT3 signaling, reactive oxygen species, NADPH oxidase, interleukin-6, starvation, tumor cell survival, HeLa cells, rapamycin, 3-methyladenine, p22phox, conditioned medium, growth factor secretion
MeSH terms: Amino Acids, Autophagy, Base Sequence, Cell Survival, Enzyme Activation, Glucose, HeLa Cells, Humans, Molecular Sequence Data, Neoplasms, Promoter Regions, Genetic, Protein Binding, Transcription, Genetic, Interleukin-6, Gene Expression Regulation, Neoplastic, Culture Media, Conditioned, Reactive Oxygen Species, NADPH Oxidases, Sirolimus, Cell Proliferation, STAT3 Transcription Factor

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

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