ArticleNature metabolism2021
Methionine synthase supports tumour tetrahydrofolate pools.
Article in Nature metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
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Who cites it
55 citing papers in PubMed, 74 citations in OpenAlex.
- Methionine Synthase Interacts With the Methionine Adenosyl-Transferase MATα2 and the DNA Methyltransferase DNMT3b in the Nucleus.Journal of inherited metabolic disease · 2026Article
- The aberration of key amino acids participated one-carbon metabolism may jeopardize genetic stability in cancer development.Cell communication and signaling : CCS · 2026Review
- Structural insights into cobalamin loading and reactivation of human methionine synthase.Nature communications · 2026Article
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- The therapeutic potential of vitamins as nutrients in food for anti-inflammatory and anti-oxidative stress in liver fibrosis diseases.Frontiers in nutrition · 2026Review
- The Methionine-Mitochondria Axis in Cancer: Metabolic Cross-Talk and Therapeutic Vulnerabilities.Current pharmacology reports · 2026Review
- Dietary methionine deprivation enhances renal resilience against ischemia-reperfusion injury in mice through modulation of glucose oxidation.Communications biology · 2025Article
- Folic acid ameliorates placental structure and function in fetal growth restriction via epigenetic modifications.Clinical epigenetics · 2025Article
- PAX3-FOXO1 Drives Targetable Cell State-Dependent Metabolic Vulnerabilities in Rhabdomyosarcoma.Cancer research · 2025Article
- Carboxy-Methylation of the Catalytic Subunit of Protein Phosphatase 2A (PP2Ac) Integrates Methionine Availability with Methionine Addicted Cancer Cell Proliferation.Biomolecules · 2025Article
- The role of BCancer & metabolism · 2025Article
- Cytosolic NADK is conditionally essential for folate-dependent nucleotide synthesis.Nature metabolism · 2025Article
- Salivary Zinc and Copper Levels Are Differentially Associated with ROS Levels in Breast Cancer Patients.International journal of molecular sciences · 2025Article
- Novel Method for the Synthesis of Hydroxycobalamin[International journal of molecular sciences · 2025Article
- Association of folate metabolism-related enzymes (MTHFR, MYD88, and TP53) and their single nucleotide polymorphisms with breast cancer susceptibility in women from Southwest China: a Bayesian network approach.Frontiers in oncology · 2025Article
- MTHFD2-mediated redox homeostasis promotes gastric cancer progression under hypoxic conditions.Redox report : communications in free radical research · 2024Article
- Pralatrexate represses the resistance of HCC cells to molecular targeted agents via the miRNA-34a/Notch pathway.Discover oncology · 2024Article
- Conditional lethality profiling reveals anticancer mechanisms of action and drug-nutrient interactions.Science advances · 2024Article
- Unveiling the Therapeutic Potential of Folate-Dependent One-Carbon Metabolism in Cancer and Neurodegeneration.International journal of molecular sciences · 2024Review
- Proteogenomic insights into the biology and treatment of pan-melanoma.Cell discovery · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Mammalian cells require activated folates to generate nucleotides for growth and division. The most abundant circulating folate species is 5-methyl tetrahydrofolate (5-methyl-THF), which is used to synthesize methionine from homocysteine via the cobalamin-dependent enzyme methionine synthase (MTR). Cobalamin deficiency traps folates as 5-methyl-THF. Here, we show using isotope tracing that MTR is only a minor source of methionine in cell culture, tissues or xenografted tumours. Instead, MTR is required for cells to avoid folate trapping and assimilate 5-methyl-THF into other folate species. Under conditions of physiological extracellular folates, genetic MTR knockout in tumour cells leads to folate trapping, purine synthesis stalling, nucleotide depletion and impaired growth in cell culture and as xenografts. These defects are rescued by free folate but not one-carbon unit supplementation. Thus, MTR plays a crucial role in liberating THF for use in one-carbon metabolism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.