2022
DOI: 10.1186/s13048-022-01022-z
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Targeting purine metabolism in ovarian cancer

Abstract: Purine, an abundant substrate in organisms, is a critical raw material for cell proliferation and an important factor for immune regulation. The purine de novo pathway and salvage pathway are tightly regulated by multiple enzymes, and dysfunction in these enzymes leads to excessive cell proliferation and immune imbalance that result in tumor progression. Maintaining the homeostasis of purine pools is an effective way to control cell growth and tumor evolution, and exploiting purine metabolism to suppress tumor… Show more

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Cited by 42 publications
(24 citation statements)
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“…Purine metabolism was mainly regulated by several enzymes and the dysfunction of these enzymes could result in immune imbalance. 36 In order to analyze the potential enzyme involved in perturbation of purine metabolism, a metabolic network containing the information of reactions, enzymes, genes and pathways was constructed. Notably, 5 0 -nucleotidase (NT5E) was the enzyme responsible for the catabolism of AMP to xanthosine.…”
Section: Discussionmentioning
confidence: 99%
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“…Purine metabolism was mainly regulated by several enzymes and the dysfunction of these enzymes could result in immune imbalance. 36 In order to analyze the potential enzyme involved in perturbation of purine metabolism, a metabolic network containing the information of reactions, enzymes, genes and pathways was constructed. Notably, 5 0 -nucleotidase (NT5E) was the enzyme responsible for the catabolism of AMP to xanthosine.…”
Section: Discussionmentioning
confidence: 99%
“…Pathway analysis results showed that purine metabolism was the most significant pathway influenced by EMB within macrophages. The purine metabolisms are essential for healthy physiological function and their disorders are closely relevant to various diseases, including inflammatory and immune process 34–36 . Abnormalities in the biosynthesis, interconversion and degradation of intermediate metabolites on the purine metabolisms could contribute to these disorders 35,37 .…”
Section: Discussionmentioning
confidence: 99%
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“…This could explain why the PPP is predicted to be upregulated alongside nucleotide metabolism for low-grade, quickly dividing ovarian cell lines. Furthermore, adenylate kinases 4 and 7 (AK4/7), which balance cellular ATP levels, are of particular focus for ovarian research (Liu et al, 2022). Model predictions show a significant increase in activity through all three reactions catalysed by AK4/7 (MAR04002, MAR04004 and MAR04480) in low-grade cell lines, and research has associated AK4-enhanced hypoxia with chemoresistance (Liu et al, 2022), a feature of low-grade ovarian tumours.…”
Section: Discussionmentioning
confidence: 99%
“…Salvage includes the recycling of nucleosides from DNA and RNA degradation, and de novo synthesis includes simple sugars and amino acids as building blocks. In general, quickly dividing cancer cells rely more on de novo nucleotide synthesis (Liu et al, 2022), which, alongside the salvage pathway, is dependent on PRPP (a product from the PPP). This could explain why the PPP is predicted to be upregulated alongside nucleotide metabolism for low-grade, quickly dividing ovarian cell lines.…”
Section: Possible Co-regulation Of the Pentose Phosphate Pathway And ...mentioning
confidence: 99%