ArticleOncoimmunology2022
Uric acid accumulation in DNA-damaged tumor cells induces NKG2D ligand expression and antitumor immunity by activating TGF-β-activated kinase 1.
Article in Oncoimmunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 15 citations in OpenAlex.
- NKGD2 Ligands (NKG2DLs) in Breast Cancer: In Silico Analysis and Narrative Review.International journal of molecular sciences · 2026Review
- Enhancement of Platinum-based Drug Sensitivity in Ovarian Cancer Cells Through Hyperthermia-induced Activation of the TGF-β1/β-Catenin Signaling Pathway.Current molecular medicine · 2026Article
- Ameliorating Acute Kidney Injury Induced by Ischemia-Reperfusion by Targeting Purine Metabolism.International journal of molecular sciences · 2025Article
- Relationship between uric acid and colon cancer risk: Dose-response analysis and mechanisms.World journal of gastrointestinal oncology · 2025Article
- Natural killer cell membrane manipulation for augmented immune synapse and anticancer efficacy.Materials today. Bio · 2025Review
- Protective role of gout against colorectal cancer: a Mendelian randomization study.Discover oncology · 2025Article
- Discrimination of superficial lymph nodes using ultrasonography and tissue metabolomics coupled with machine learning.Frontiers in oncology · 2025Article
- Unraveling the breast cancer tumor microenvironment: crucial factors influencing natural killer cell function and therapeutic strategies.International journal of biological sciences · 2025Review
- Dual roles of innate immune cells and cytokines in shaping the breast cancer microenvironment.Frontiers in immunology · 2025Review
- Impact of gout on colorectal cancer and its survival: a two-sample Mendelian randomization study.Discover oncology · 2024Article
- Article
- Review
- Relationship between rs4349859 and rs116488202 polymorphisms close to MHC-I region and serum urate levels in patients with gout.Molecular biology reports · 2023Article
- Stem cell-assisted enzyme/prodrug therapy makes drug-resistant ovarian cancer cells vulnerable to natural killer cells through upregulation of NKG2D ligands.Medical oncology (Northwood, London, England) · 2023Article
- A Polynesian-specific copy number variant encompassing the MICA gene associates with gout.Human molecular genetics · 2022Article
- A Novel Purine and Uric Metabolism Signature Predicting the Prognosis of Hepatocellular Carcinoma.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA damage by genotoxic drugs such as gemcitabine and 5-fluorouracil (5-FU) activates the ataxia telangiectasia, mutated (ATM)-Chk pathway and induces the expression of NKG2D ligands such as the MHC class I-related chain A and B (MICA/B). The mechanisms underlying this remain incompletely understood. Here we report that xanthine oxidoreductase (XOR), a rate-limiting enzyme that produces uric acid in the purine catabolism pathway, promotes DNA damage-induced MICA/B expression. Inhibition of the ATM-Chk pathway blocks genotoxic drug-induced uric acid production, TGF-β-activated kinase 1 (TAK1) activation, ERK phosphorylation, and MICA/B expression. Inhibition of uric acid production by the XOR inhibitor allopurinol blocks DNA damage-induced TAK1 activation and MICA/B expression in genotoxic drug-treated cells. Exogenous uric acid activates TAK1, NF-κB, and the MAP kinase pathway. TAK1 inhibition blocks gemcitabine- and uric acid-induced MAP kinase activation and MICA/B expression. Exogenous uric acid in its salt form, monosodium urate (MSU), induces MICA/B expression and sensitizes tumor cells to NK cell killing. MSU immunization with irradiated murine breast cancer cell line RCAS-Neu retards breast cancer growth in syngeneic breast cancer models and delays breast cancer development in a somatic breast cancer model. Our study suggests that uric acid accumulation plays an important role in activating TAK1, inducing DNA damage-induced MICA/B expression, and enhancing antitumor immunity.
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