One-carbon metabolism in cancer

Newman, Alice C.; Maddocks, Oliver D.K.

doi:10.1038/bjc.2017.118

Cited by 365 publications

(334 citation statements)

References 54 publications

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“…Cancer cells require high quantities of energy and anabolic resources to support their rapid cell division; therefore, their key metabolic pathways are altered. 34,35 Notably, we observed that elevated levels of the purine catabolic pathway metabolites hypoxanthine and uric acid were associated with AAs with BLCA. 32,33 Overall, our platform was able to identify altered metabolites and associated pathways in AA BLCA versus EA BLCA.…”

Section: Discussionmentioning

confidence: 76%

“…This metabolic pathway supports several physiological processes that provide one-carbon units for methylation reactions, nucleotide synthesis, amino acid homeostasis, and reductive metabolism, which support the high proliferation of cancer cells. 34,35 Notably, we observed that elevated levels of the purine catabolic pathway metabolites hypoxanthine and uric acid were associated with AAs with BLCA. Recent studies have demonstrated that elevated levels of uric acid in serum are associated with greater cancer risk, recurrence, and mortality in colorectal, breast, and prostate cancers, [36][37][38] and its proinflammatory properties may play a role in BLCA pathogenesis in AAs.…”

Section: Discussionmentioning

confidence: 76%

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Large‐scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival

Vantaku

Donepudi

Piyarathna

et al. 2019

Cancer

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BACKGROUND: African Americans (AAs) experience a disproportionally high rate of bladder cancer (BLCA) deaths even though their incidence rates are lower than those of other patient groups. Using a metabolomics approach, this study investigated how AA BLCA may differ molecularly from European Americans (EAs) BLCA, and it examined serum samples from patients with BLCA with the aim of identifying druggable metabolic pathways in AA patients. METHODS: Targeted metabolomics was applied to measure more than 300 metabolites in serum samples from 2 independent cohorts of EA and AA patients with BLCA and healthy EA and AA controls via liquid chromatography-mass spectrometry, and this was followed by the identification of altered metabolic pathways with a focus on AA BLCA. A subset of the differential metabolites was validated via absolute quantification with the Biocrates AbsoluteIDQ p180 kit. The clinical significance of the findings was further examined in The Cancer Genomic Atlas BLCA data set. RESULTS: Fifty-three metabolites, mainly related to amino acid, lipid, and nucleotide metabolism, were identified that showed significant differences in abundance between AA and EA BLCA. For example, the levels of taurine, glutamine, glutamate, aspartate, and serine were elevated in serum samples from AA patients versus EA patients. By mapping these metabolites to genes, this study identified significant relations with regulators of metabolism such as malic enzyme 3, prolyl 3-hydroxylase 2, and lysine demethylase 2A that predicted patient survival exclusively in AA patients with BLCA. CONCLUSIONS: This metabolic profile of serum samples might be used to assess risk progression in AA BLCA. These first-in-field findings describe metabolic alterations in AA BLCA and emphasize a potential biological basis for BLCA health disparities. Cancer 2019;125:921-932.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 76%

Large‐scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival

Vantaku

Donepudi

Piyarathna

et al. 2019

Cancer

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“…Some previous studies have associated carbon metabolism with carcinogenesis, mainly due to its role in DNA synthesis (Newman and Maddocks, ). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Another pathway of intense interest in cancer in recent years is one‐carbon metabolism, mainly due to the need of cancer cells to support enhanced proliferation and survival (Ducker and Rabinowitz, ; Newman and Maddocks, ). In this study, multiple pathway metabolites were significantly altered (glycine, sarcosine, SAH, methionine, homocysteine; Fig.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic profiling of human lung tumor tissues – nucleotide metabolism as a candidate for therapeutic interventions and biomarkers

et al. 2018

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Although metabolomics has attracted considerable attention in the field of lung cancer (LC) detection and management, only a very limited number of works have applied it to tissues. As such, the aim of this study was the thorough analysis of metabolic profiles of relevant LC tissues, including the most important histological subtypes (adenocarcinoma and squamous cell lung carcinoma). Mass spectrometry‐based metabolomics, along with genetic expression and histological analyses, were performed as part of this study, the widest to date, to identify metabolic alterations in tumors of the most relevant histological subtypes in lung. A total of 136 lung tissue samples were analyzed and 851 metabolites were identified through metabolomic analysis. Our data show the existence of a clear metabolic alteration not only between tumor vs. nonmalignant tissue in each patient, but also inherently intrinsic changes in both AC and SCC. Significant changes were observed in the most relevant biochemical pathways, and nucleotide metabolism showed an important number of metabolites with high predictive capability values. The present study provides a detailed analysis of the metabolomic changes taking place in relevant biochemical pathways of the most important histological subtypes of LC, which can be used as biomarkers and also to identify novel targets.

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“…It has been hypothesized that this defect in cancerous, as compared to normal, cells could be used for therapeutic purpose 9–11 . A methionine-free diet or methionine-deprived total parenteral nutrition causes regression of a variety of animal tumors 12 . It has also been suggested that vegan diets, containing relatively lower methionine, may be a useful nutritional strategy controlling for cancer growth 13 .…”

Section: Introductionmentioning

confidence: 99%

Genetic variants in RUNX3, AMD1 and MSRA in the methionine metabolic pathway and survival in nonsmall cell lung cancer patients

Chen

Liu

et al. 2019

Intl Journal of Cancer

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Abnormal methionine dependence in cancer cells has led to methionine restriction as a potential therapeutic strategy. We hypothesized that genetic variants involved in methionine-metabolic genes are associated with survival in non-small cell lung cancer (NSCLC) patients. Therefore, we investigated associations of 16,378 common single-nucleotide polymorphisms (SNPs) in 97 methionine-metabolic pathway genes with overall survival (OS) in NSCLC patients using genotyping data from two published genome-wide association study (GWAS) datasets. In the single-locus analysis, 1,005 SNPs were significantly associated with NSCLC OS (P < 0.05 and false-positive report probability < 0.2) in the discovery dataset. Three SNPs (RUNX3 rs7553295G>T, AMD1 rs1279590G>A and MSRA rs73534533C>A) were replicated in the validation dataset and their meta-analysis showed that adjusted hazards ratio [HR] of 0.82 [95% confidence interval (CI) =0.75-0.89] and Pmeta=2.86 x 10−6, 0.81 (0.73-0.91) and Pmeta=4.63 x 10−4, and 0.77 (0.68-0.89) and Pmeta=2.07 x 10−4, respectively). A genetics score of protective genotypes of these three SNPs revealed an increased OS in a dose-response manner (Ptrend <.0001). Further expression quantitative trait loci (eQTL) analysis showed significant associations between these genotypes and gene mRNA expression levels. Moreover, differential expression analysis further supported a tumor-suppressive effect of MSRA, with lower mRNA levels in both lung squamous carcinoma and adenocarcinoma (P <.0001 and <.0001, respectively) than in adjacent normal tissues. Additionally, low mutation rates of these three genes indicated the critical roles of these functional SNPs in cancer progression. Taken together, these genetic variants of methionine-metabolic pathway genes may be promising predictors of survival in NSCLC patients.

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One-carbon metabolism in cancer

Cited by 365 publications

References 54 publications

Large‐scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival

Large‐scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival

Metabolomic profiling of human lung tumor tissues – nucleotide metabolism as a candidate for therapeutic interventions and biomarkers

Genetic variants in RUNX3, AMD1 and MSRA in the methionine metabolic pathway and survival in nonsmall cell lung cancer patients

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