ArticleThe EMBO journal2021
Nuclear IL-33/SMAD signaling axis promotes cancer development in chronic inflammation.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- IL-33/ST2 immunobiology in coronary artery disease: A systematic review and meta-analysis.Frontiers in cardiovascular medicine · 2022Pooled it
- Oxidative balance score, genetic susceptibility, and the risk of pancreatic cancer: a population-based cohort study.Nutrition journal · 2026Article
- Fibroblast-derived alarmin promotes oral wound healing by activating regulatory T cells that relay pro-angiogenic and anti-inflammatory responses.Cell reports · 2026Article
- Critical role of interleukin-33 in pathogenesis and progression of metabolic dysfunction-associated steatotic liver disease.Frontiers in medicine · 2026Review
- Targeting the gut-pancreatic axis: microbial modulation of immunotherapy in pancreatic cancer.Frontiers in immunology · 2026Review
- Interleukin-33 at the intersection of inflammation and repair.Frontiers in allergy · 2026Review
- Plasticity and Functional Heterogeneity of Cancer-Associated Fibroblasts.Cancer research · 2025Review
- Intestinal IL-33 promotes microbiota-derived trimethylamine N -oxide synthesis and drives metabolic dysfunction-associated steatotic liver disease progression by exerting dual regulation on HIF-1α.Hepatology (Baltimore, Md.) · 2025Article
- Hepatitis B virus promotes liver cancer by modulating the immune response to environmental carcinogens.Nature communications · 2025Article
- Tropisetron Suppresses Chronic Pancreatitis and Pancreatic Cancer by Blocking Interleukin 33 Expression.Cancers · 2025Article
- Investigating the role of inflammatory cytokines in mediating the effect of gut microbiota on gastrointestinal cancers: a mendelian randomization study.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- Interleukin-33 (IL-33) promotes DNA damage-resistance in lung cancer.Cell death & disease · 2025Article
- Innovation through imitation: IL-33 decoys show promise in pulmonary fibrosis.The Journal of pharmacology and experimental therapeutics · 2025Article
- Interleukins as a potential link between obstructive sleep apnea and renal cell carcinoma.Contemporary oncology (Poznan, Poland) · 2025Review
- Therapeutic targeting of full-length interleukin-33 protein levels with cell-permeable decoy peptides attenuates fibrosis in the bleomycin model in vivo.The Journal of pharmacology and experimental therapeutics · 2025Article
- Research progress on the mechanisms of endogenous neural stem cell differentiation in spinal cord injury repair.Frontiers in cellular neuroscience · 2025Review
- Exogenous IL-33 promotes tumor immunity via macroscopic regulation of ILC2s.Scientific reports · 2024Article
- Oncogenic KRAS-Dependent Stromal Interleukin-33 Directs the Pancreatic Microenvironment to Promote Tumor Growth.Cancer discovery · 2024Article
- Pancreatic stellate cells and the interleukin family: Linking fibrosis and immunity to pancreatic ductal adenocarcinoma (Review).Molecular medicine reports · 2024Review
- Statin prevents cancer development in chronic inflammation by blocking interleukin 33 expression.Nature communications · 2024Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Interleukin (IL)-33 cytokine plays a critical role in allergic diseases and cancer. IL-33 also has a nuclear localization signal. However, the nuclear function of IL-33 and its impact on cancer is unknown. Here, we demonstrate that nuclear IL-33-mediated activation of SMAD signaling pathway in epithelial cells is essential for cancer development in chronic inflammation. Using RNA and ChIP sequencing, we found that nuclear IL-33 repressed the expression of an inhibitory SMAD, Smad6, by interacting with its transcription factor, RUNX2. IL-33 was highly expressed in the skin and pancreatic epithelial cells in chronic inflammation, leading to a markedly repressed Smad6 expression as well as dramatically upregulated p-SMAD2/3 and p-SMAD1/5 in the epithelial cells. Blocking TGF-β/SMAD signaling attenuated the IL-33-induced cell proliferation in vitro and inhibited IL-33-dependent epidermal hyperplasia and skin cancer development in vivo. IL-33 and SMAD signaling were upregulated in human skin cancer, pancreatitis, and pancreatitis-associated pancreatic cancer. Collectively, our findings reveal that nuclear IL-33/SMAD signaling is a cell-autonomous tumor-promoting axis in chronic inflammation, which can be targeted by small-molecule inhibitors for cancer treatment and prevention.
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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.