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RSS FeedsIJMS, Vol. 23, Pages 5774: 4-Pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR)—A Novel Oncometabolite Modulating Cancer-Endothelial Interactions in Breast Cancer Metastasis (International Journal of Molecular Sciences)

 
 

21 may 2022 10:50:24

 
IJMS, Vol. 23, Pages 5774: 4-Pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR)—A Novel Oncometabolite Modulating Cancer-Endothelial Interactions in Breast Cancer Metastasis (International Journal of Molecular Sciences)
 


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.


 
62 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
IJMS, Vol. 23, Pages 5772: Venom Peptide Toxins Targeting the Outer Pore Region of Transient Receptor Potential Vanilloid 1 in Pain: Implications for Analgesic Drug Development (International Journal of Molecular Sciences)
IJMS, Vol. 23, Pages 5771: Therapeutic Effect of Platelet-Rich Plasma Improves Bladder Overactivity in the Pathogenesis of Ketamine-Induced Ulcerative Cystitis in a Rat Model (International Journal of Molecular Sciences)
 
 
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