ArticleInternational journal of molecular sciences2022
4-Pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR)-A Novel Oncometabolite Modulating Cancer-Endothelial Interactions in Breast Cancer Metastasis.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 5 citations in OpenAlex.
- Synthesis, characterization and bioactivity of new pyridine-2(H)-one, nicotinonitrile, and furo[2,3-b]pyridine derivatives.Molecular diversity · 2025Article
- Synthesis, Detection, and Metabolism of Pyridone Ribosides, Products of NAD Overoxidation.Chemical research in toxicology · 2024Article
- Elevated Plasma Concentration of 4-Pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) Highlights Malignancy of Renal Cell Carcinoma.International journal of molecular sciences · 2024Article
- Defining NAD(P)(H) Catabolism.Nutrients · 2023Review
- Conformational Preferences of Pyridone Adenine Dinucleotides from Molecular Dynamics Simulations.International journal of molecular sciences · 2022Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The accumulation of specific metabolic intermediates is known to promote cancer progression. We analyzed the role of 4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR), a nucleotide metabolite that accumulates in the blood of cancer patients, using the 4T1 murine in vivo breast cancer model, and cultured cancer (4T1) and endothelial cells (ECs) for in vitro studies. In vivo studies demonstrated that 4PYR facilitated lung metastasis without affecting primary tumor growth. In vitro studies demonstrated that 4PYR affected extracellular adenine nucleotide metabolism and the intracellular energy status in ECs, shifting catabolite patterns toward the accumulation of extracellular inosine, and leading to the increased permeability of lung ECs. These changes prevailed over the direct effect of 4PYR on 4T1 cells that reduced their invasive potential through 4PYR-induced modulation of the CD73-adenosine axis. We conclude that 4PYR is an oncometabolite that affects later stages of the metastatic cascade by acting specifically through the regulation of EC permeability and metabolic controls of inflammation.
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