ArticleRoyal Society open science2017
Modelling pyruvate dehydrogenase under hypoxia and its role in cancer metabolism.
Article in Royal Society open science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Machine learning and metabolic modeling-based identification of hypoxia-driven metabolic signatures in pediatric cancers.Frontiers in pharmacology · 2026Article
- Biochemical Aspects That Lead to Abusive Use of Trimetazidine in Performance Athletes: A Mini-Review.International journal of molecular sciences · 2024Review
- The effect of lactate dehydrogenase inhibitors on proliferation, motility and invasion of breast cancer cellsMolecular medicine reports · 2024Article
- Comparing mechanism-based and machine learning models for predicting the effects of glucose accessibility on tumor cell proliferation.Scientific reports · 2023Article
- Machine Learning Methods for Survival Analysis with Clinical and Transcriptomics Data of Breast Cancer.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Methods for Stratification and Validation Cohorts: A Scoping Review.Journal of personalized medicine · 2022Article
- Dihydrolipoamide dehydrogenase, pyruvate oxidation, and acetylation-dependent mechanisms intersecting drug iatrogenesis.Cellular and molecular life sciences : CMLS · 2021Review
- Allele-Specific MicroRNA-Mediated Regulation of a Glycolysis Gatekeeper PDK1 in Cancer Metabolism.Cancers · 2021Article
- Mitochondrial Dysfunction: Cause or Consequence of Vascular Calcification?Frontiers in cell and developmental biology · 2021Review
- Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer.Journal of experimental & clinical cancer research : CR · 2020Review
- Oncogene inference optimization using constraint-based modelling incorporated with protein expression in normal and tumour tissues.Royal Society open science · 2020Article
- Human Systems Biology and Metabolic Modelling: A Review-From Disease Metabolism to Precision Medicine.BioMed research international · 2019Review
- CiliateGEM: an open-project and a tool for predictions of ciliate metabolic variations and experimental condition design.BMC bioinformatics · 2018Article
- The poly-omics of ageing through individual-based metabolic modelling.BMC bioinformatics · 2018Article
- In silico engineering ofPeerJ · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolism is the only biological system that can be fully modelled at genome scale. As a result, metabolic models have been increasingly used to study the molecular mechanisms of various diseases. Hypoxia, a low-oxygen tension, is a well-known characteristic of many cancer cells. Pyruvate dehydrogenase (PDH) controls the flux of metabolites between glycolysis and the tricarboxylic acid cycle and is a key enzyme in metabolic reprogramming in cancer metabolism. Here, we develop and manually curate a constraint-based metabolic model to investigate the mechanism of pyruvate dehydrogenase under hypoxia. Our results characterize the activity of pyruvate dehydrogenase and its decline during hypoxia. This results in lactate accumulation, consistent with recent hypoxia studies and a well-known feature in cancer metabolism. We apply machine-learning techniques on the flux datasets to identify reactions that drive these variations. We also identify distinct features on the structure of the variables and individual metabolic components in the switch from normoxia to hypoxia. Our results provide a framework for future studies by integrating multi-omics data to predict condition-specific metabolic phenotypes under hypoxia.
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