ArticleNature metabolism2021
Methionine synthase is essential for cancer cell proliferation in physiological folate environments.
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 78 papers.
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Who cites it
78 citing papers in PubMed, 103 citations in OpenAlex.
- A guide to B cell metabolism.Nature reviews. Immunology · 2026Review
- Mitochondrial depolarization stabilizes the vitamin BProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Physiological folate levels constrain nucleotide synthesis and increase dependence on nucleotide salvage.bioRxiv : the preprint server for biology · 2026Article
- Functional genomics and proteomics identify Folate Carrier SLC19A1 as a predictor of pralatrexate sensitivity in diverse T-cell lymphoma models.Molecular cancer therapeutics · 2026Article
- Sulfur-Containing Amino Acids: The Conversion Process from Product to Substrate.International journal of molecular sciences · 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
- Association between Vitamin B12 Levels and Colon Cancer Survival: A Global Network Study.Cancer research communications · 2026Article
- SLC46A1 deficiency-mediated folate restriction suppresses colorectal cancer progression through epigenetic-transcriptional reprogramming.Cell death & disease · 2026Article
- Article
- The Methionine-Mitochondria Axis in Cancer: Metabolic Cross-Talk and Therapeutic Vulnerabilities.Current pharmacology reports · 2026Review
- Mucosal-associated invariant T cells recognize a tumor-derived metabolite in the DNA synthesis pathway.Frontiers in immunology · 2026Article
- Mitochondrial depolarization stabilizes the vitamin B12 chaperone MMADHC in the cytosol to increase MTR activity.bioRxiv : the preprint server for biology · 2025Article
- One-carbon metabolism in cancer: moonlighting functions of metabolic enzymes and anti-tumor therapy.Cancer metastasis reviews · 2025Review
- PAX3-FOXO1 Drives Targetable Cell State-Dependent Metabolic Vulnerabilities in Rhabdomyosarcoma.Cancer research · 2025Article
- Renal insulin-like growth factor binding-protein 7 is a critical promoter of progressive diabetic kidney disease.Nature communications · 2025Article
- Distinct S-adenosylmethionine synthases link phosphatidylcholine to mitochondrial function and stress survival.PLoS biology · 2025Article
- An atlas of ferroptosis-induced secretomes.Cell death and differentiation · 2025Article
- Integrating functional genomics and proteomics identifies Folate Carrier SLC19A1 as a predictor of pralatrexate sensitivity in T-cell lymphoma.bioRxiv : the preprint server for biology · 2025Article
- Carboxy-Methylation of the Catalytic Subunit of Protein Phosphatase 2A (PP2Ac) Integrates Methionine Availability with Methionine Addicted Cancer Cell Proliferation.Biomolecules · 2025Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Folate metabolism can be an effective target for cancer treatment. However, standard cell culture conditions utilize folic acid, a non-physiological folate source for most tissues. We find that the enzyme that couples folate and methionine metabolic cycles, methionine synthase, is required for cancer cell proliferation and tumour growth when 5-methyl tetrahydrofolate (THF), the major folate found in circulation, is the extracellular folate source. In such physiological conditions, methionine synthase incorporates 5-methyl THF into the folate cycle to maintain intracellular levels of the folates needed for nucleotide production. 5-methyl THF can sustain intracellular folate metabolism in the absence of folic acid. Therefore, cells exposed to 5-methyl THF are more resistant to methotrexate, an antifolate drug that specifically blocks folic acid incorporation into the folate cycle. Together, these data argue that the environmental folate source has a profound effect on folate metabolism, determining how both folate cycle enzymes and antifolate drugs impact proliferation.
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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.