ArticleOncotarget2016
Hyperinsulinemia enhances interleukin-17-induced inflammation to promote prostate cancer development in obese mice through inhibiting glycogen synthase kinase 3-mediated phosphorylation and degradation of interleukin-17 receptor.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Serum C-peptide concentration and prostate cancer: A meta-analysis of observational studies.Medicine · 2018Pooled it
- Review
- DYRK kinases phosphorylate IL-17RA at S801.Serican journal of medicine · 2026Article
- Article
- IL-17A Drives Oxidative Stress and Cell Growth in A549 Lung Epithelial Cells: Potential Protective Action of Oleuropein.Nutrients · 2024Article
- Key players of immunosuppression in epithelial malignancies: Tumor-infiltrating myeloid cells and γδ T cells.Cancer reports (Hoboken, N.J.) · 2024Review
- SCFBiomedicines · 2024Article
- The role of interleukin-17 in inflammation-related cancers.Frontiers in immunology · 2024Review
- Role of IL-17A and IL-17RA in Prostate Cancer with Lymph Nodes Metastasis: Expression Patterns and Clinical Significance.Cancers · 2023Article
- Defect of IL17 Signaling, but Not Centrinone, Inhibits the Development of Psoriasis and Skin Papilloma in Mouse Models.Biomedicines · 2022Article
- Harnessing Antitumor CD4Cancers · 2022Review
- Article
- A Novel Controlled PTEN-Knockout Mouse Model for Prostate Cancer Study.Frontiers in molecular biosciences · 2021Article
- Review
- Prostate carcinogenesis: inflammatory storms.Nature reviews. Cancer · 2020Review
- Targeting the interleukin-17 immune axis for cancer immunotherapy.The Journal of experimental medicine · 2020Review
- Expression Levels of IL-17A, IL-17F, IL-17RA, and IL-17RC in Prostate Cancer with Taking into Account the Histological Grade according to Gleason Scale in Comparison to Benign Prostatic Hyperplasia: In Search of New Therapeutic Options.Journal of immunology research · 2020Article
- Main Inflammatory Cells and Potentials of Anti-Inflammatory Agents in Prostate Cancer.Cancers · 2019Review
- Th17 cells promote tumor growth in an immunocompetent orthotopic mouse model of prostate cancer.American journal of clinical and experimental urology · 2019Article
- Interleukin-17 Promotes Migration and Invasion of Human Cancer Cells Through Upregulation of MTA1 Expression.Frontiers in oncology · 2019Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Interleukin-17 (IL-17) plays important roles in inflammation, autoimmune diseases, and some cancers. Obese people are in a chronic inflammatory state with increased serum levels of IL-17, insulin, and insulin-like growth factor 1 (IGF1). How these factors contribute to the chronic inflammatory status that promotes development of aggressive prostate cancer in obese men is largely unknown. We found that, in obese mice, hyperinsulinemia enhanced IL-17-induced expression of downstream proinflammatory genes with increased levels of IL-17 receptor A (IL-17RA), resulting in development of more invasive prostate cancer. Glycogen synthase kinase 3 (GSK3) constitutively bound to and phosphorylated IL-17RA at T780, leading to ubiquitination and proteasome-mediated degradation of IL-17RA, thus inhibiting IL-17-mediated inflammation. IL-17RA phosphorylation was reduced, while the IL-17RA levels were increased in the proliferative human prostate cancer cells compared to the normal cells. Insulin and IGF1 enhanced IL-17-induced inflammatory responses through suppressing GSK3, which was shown in the cultured cell lines in vitro and obese mouse models of prostate cancer in vivo. These findings reveal a mechanism underlying the intensified inflammation in obesity and obesity-associated development of aggressive prostate cancer, suggesting that targeting GSK3 may be a potential therapeutic approach to suppress IL-17-mediated inflammation in the prevention and treatment of prostate cancer, particularly in obese men.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.