ArticleNeoplasia (New York, N.Y.)2005
A3 adenosine receptors modulate hypoxia-inducible factor-1alpha expression in human A375 melanoma cells.
Article in Neoplasia (New York, N.Y.), 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
38 citing papers in PubMed, 84 citations in OpenAlex.
- A3 Adenosine Receptor Agonists as Multisystem Disease Modifiers: From Molecular Signaling to Clinical Translation.Biomolecules · 2026Review
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- Adenosine AFEBS open bio · 2025Article
- Adenosine and Its Receptors in the Pathogenesis and Treatment of Inflammatory Skin Diseases.International journal of molecular sciences · 2024Review
- Structure-Activity Relationship of Truncated 2,8-Disubstituted-Adenosine Derivatives as Dual AJournal of medicinal chemistry · 2023Article
- Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function.Cancer immunology research · 2023Article
- Immunogenetic metabolomics revealed key enzymes that modulate CAR-T metabolism and function.bioRxiv : the preprint server for biology · 2023Article
- Sentinel Lymph Node Gene Expression Signature Predicts Recurrence-Free Survival in Cutaneous Melanoma.Cancers · 2022Article
- Adenosine Kinase on Deoxyribonucleic Acid Methylation: Adenosine Receptor-Independent Pathway inFrontiers in pharmacology · 2022Review
- Purinergic signaling in the modulation of redox biology.Redox biology · 2021Review
- Review
- CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers.Frontiers in immunology · 2020Review
- Role of purines in regulation of metabolic reprogramming.Purinergic signalling · 2019Review
- Involvement of AJournal of molecular neuroscience : MN · 2019Article
- Adenosine Kinase Deficiency Increases Susceptibility to a Carcinogen.Journal of caffeine and adenosine research · 2019Article
- Targeting Adenosine in Cancer Immunotherapy to Enhance T-Cell Function.Frontiers in immunology · 2019Review
- Targeting Adenosine Receptor Signaling in Cancer Immunotherapy.International journal of molecular sciences · 2018Review
- Adenosinergic signaling as a target for natural killer cell immunotherapy.Journal of molecular medicine (Berlin, Germany) · 2018Review
- AMedicinal research reviews · 2018Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factor-1 (HIF-1) is a key regulator of genes crucial to many aspects of cancer biology. The purine nucleoside, adenosine, accumulates within many tissues under hypoxic conditions, including that of tumors. Because the levels of both HIF-1 and adenosine are elevated within the hypoxic environment of solid tumors, we investigated whether adenosine may regulate HIF-1. Here we show that, under hypoxic conditions (< 2% O2), adenosine upregulates HIF-1alpha protein expression in a dose-dependent and time-dependent manner, exclusively through the A3 receptor subtype. The response to adenosine was generated at the cell surface because the inhibition of A3 receptor expression, by using small interfering RNA, abolished nucleoside effects. A3 receptor stimulation in hypoxia also increases angiopoietin-2 (Ang-2) protein accumulation through the induction of HIF-1alpha. In particular, we found that A3 receptor stimulation activates p44/p42 and p38 mitogen-activated protein kinases, which are required for A3-induced increase of HIF-1alpha and Ang-2. Collectively, these results suggest a cooperation between hypoxic and adenosine signals that ultimately may lead to the increase in HIF-1-mediated effects in cancer cells.
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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.