ArticleCell reports. Medicine2023
Adenosine A2A receptor is a tumor suppressor of NASH-associated hepatocellular carcinoma.
Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
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- Purinergic signaling in osteoarthritis: Mechanistic insights into pathogenesis and therapeutic targeting.Genes & diseases · 2026Review
- The P2X4-P2X7 purinergic axis in alcohol-related liver disease: from fibrogenesis to immunotherapy resistance.Purinergic signalling · 2026Review
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- A2AR as a key target for immune microenvironment remodeling in prostate cancer.Translational oncology · 2026Article
- Transforming Liver Cancer Therapy: Integrating Molecular Profiling with Precision and Transplant-Based Care.Cancers · 2025Review
- Mesenchymal Stem Cell-Mediated Targeted Drug Delivery Systems for Hepatocellular Carcinoma: Current Advances and Future Directions.Bioengineering (Basel, Switzerland) · 2025Review
- Caffeine: a potential mechanism for anti-obesity.Purinergic signalling · 2025Review
- Deciphering adenosine signaling in hepatocellular carcinoma: Pathways, prognostic models, and therapeutic implications.Clinical and molecular hepatology · 2025Review
- Research progress of CD73-adenosine signaling regulating hepatocellular carcinoma through tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2025Review
- Liver diseases: epidemiology, causes, trends and predictions.Signal transduction and targeted therapy · 2025Review
- Next-Generation Immunotherapy for Hepatocellular Carcinoma: Mechanisms of Resistance and Novel Treatment Approaches.Cancers · 2025Review
- Identification of galangin as a therapeutic candidate for primary biliary cholangitis via systematic druggable genome-wide Mendelian randomization analysis and experimental validation.Frontiers in pharmacology · 2025Article
- Adenosine receptors on the immuno-oncology expressway: TIME, perspectives, and translation.Frontiers in immunology · 2025Review
- New MiniPromoter Ple389 (ADORA2A) drives selective expression in medium spiny neurons in mice and non-human primates.Scientific reports · 2024Article
- Surgical Implications for Nonalcoholic Steatohepatitis-Related Hepatocellular Carcinoma.Cancers · 2024Review
- The landscape of cancer-rewired GPCR signaling axes.Cell genomics · 2024Article
- Clinical and Biologic Correlates of ADORA2A Transcriptomic Expression in Cancer.International journal of molecular sciences · 2024Article
- Activation of hepatic adenosine A1 receptor ameliorates MASH via inhibiting SREBPs maturation.Cell reports. Medicine · 2024Article
- The different effects of four adenosine receptors in liver fibrosis.Frontiers in pharmacology · 2024Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
Inhibition of adenosine A2A receptor (A2AR) is a promising approach for cancer immunotherapy currently evaluated in several clinical trials. We here report that anti-obesogenic and anti-inflammatory functions of A2AR, however, significantly restrain hepatocellular carcinoma (HCC) development. Adora2a deletion in mice triggers obesity, non-alcoholic steatohepatitis (NASH), and systemic inflammation, leading to spontaneous HCC and promoting dimethylbenzyl-anthracene (DMBA)- or diethylnitrosamine (DEN)-induced HCC. Conditional Adora2a deletion reveals critical roles of myeloid and hepatocyte-derived A2AR signaling in restraining HCC by limiting hepatic inflammation and steatosis. Remarkably, the impact of A2AR pharmacological blockade on HCC development is dependent on pre-existing NASH. In support of our animal studies, low ADORA2A gene expression in human HCC is associated with cirrhosis, hepatic inflammation, and poor survival. Together, our study uncovers a previously unappreciated tumor-suppressive function for A2AR in the liver and suggests caution in the use of A2AR antagonists in patients with NASH and NASH-associated HCC.
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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.