Cycling back to folate metabolism in cancer

Warburg, O., Wind, F. & Negelein, E. The metabolism of tumors in the body. J. Gen. Physiol. 8, 519–530 (1927).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).

Article  CAS  PubMed  Google Scholar 

Farber, S. & Diamond, L. K. Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid. N. Engl. J. Med. 238, 787–793 (1948).

Article  CAS  PubMed  Google Scholar 

Osborn, M. J., Freeman, M. & Huennekens, F. M. Inhibition of dihydrofolic reductase by aminopterin and amethopterin. Proc. Soc. Exp. Biol. Med. 97, 429–431 (1958).

Article  CAS  PubMed  Google Scholar 

Schalinske, K. L. & Steele, R. D. Methotrexate alters carbon flow through the hepatic folate-dependent one-carbon pool in rats. Carcinogenesis 17, 1695–1700 (1996).

Article  CAS  PubMed  Google Scholar 

Huennekens, F. M., Duffy, T. H. & Vitols, K. S. Folic acid metabolism and its disruption by pharmacologic agents. NCI Monogr. 5, 1–8 (1987).

Google Scholar 

Chabner, B. A. & Roberts, T. G. Jr. Timeline: chemotherapy and the war on cancer. Nat. Rev. Cancer 5, 65–72 (2005).

Article  CAS  PubMed  Google Scholar 

Sedillo, J. C. & Cryns, V. L. Targeting the methionine addiction of cancer. Am. J. Cancer Res. 12, 2249–2276 (2022).

CAS  PubMed  PubMed Central  Google Scholar 

Parsa, S. et al. The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing. Nat. Cancer 1, 653–664 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Geeraerts, S. L., Heylen, E., De Keersmaecker, K. & Kampen, K. R. The ins and outs of serine and glycine metabolism in cancer. Nat. Metab. 3, 131–141 (2021).

Article  CAS  PubMed  Google Scholar 

Yang, M. & Vousden, K. H. Serine and one-carbon metabolism in cancer. Nat. Rev. Cancer 16, 650–662 (2016).

Article  CAS  PubMed  Google Scholar 

Ducker, G. S. & Rabinowitz, J. D. One-carbon metabolism in health and disease. Cell Metab. 25, 27–42 (2017).

Article  CAS  PubMed  Google Scholar 

Pfeiffer, C. M. et al. Folate status and concentrations of serum folate forms in the US population: National Health and Nutrition Examination Survey 2011–2. Br. J. Nutr. 113, 1965–1977 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chandler, C. J., Wang, T. T. & Halsted, C. H. Pteroylpolyglutamate hydrolase from human jejunal brush borders. Purification and characterization. J. Biol. Chem. 261, 928–933 (1986).

Article  CAS  PubMed  Google Scholar 

Wright, A. J., Dainty, J. R. & Finglas, P. M. Folic acid metabolism in human subjects revisited: potential implications for proposed mandatory folic acid fortification in the UK. Br. J. Nutr. 98, 667–675 (2007).

Article  CAS  PubMed  Google Scholar 

Sullivan, M. R. et al. Methionine synthase is essential for cancer cell proliferation in physiological folate environments. Nat. Metab. 3, 1500–1511 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ghergurovich, J. M. et al. Methionine synthase supports tumour tetrahydrofolate pools. Nat. Metab. 3, 1512–1520 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tucker, E. J. et al. Mutations in MTFMT underlie a human disorder of formylation causing impaired mitochondrial translation. Cell Metab. 14, 428–434 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Minton, D. R. et al. Serine catabolism by SHMT2 is required for proper mitochondrial translation initiation and maintenance of formylmethionyl-tRNAs. Mol. Cell 69, 610–621 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ducker, G. S. et al. Reversal of cytosolic one-carbon flux compensates for loss of the mitochondrial folate pathway. Cell Metab. 23, 1140–1153 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zheng, Y. et al. Mitochondrial one-carbon pathway supports cytosolic folate integrity in cancer cells. Cell 175, 1546–1560 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brosnan, M. E. & Brosnan, J. T. Formate: the neglected member of one-carbon metabolism. Annu. Rev. Nutr. 36, 369–388 (2016).

Article  CAS  PubMed  Google Scholar 

Meiser, J. et al. Serine one-carbon catabolism with formate overflow. Sci. Adv. 2, e1601273 (2016).

Article  PubMed  PubMed Central  Google Scholar 

Barlowe, C. K. & Appling, D. R. In vitro evidence for the involvement of mitochondrial folate metabolism in the supply of cytoplasmic one-carbon units. Biofactors 1, 171–176 (1988).

CAS  PubMed  Google Scholar 

Kikuchi, G., Motokawa, Y., Yoshida, T. & Hiraga, K. Glycine cleavage system: reaction mechanism, physiological significance, and hyperglycinemia. Proc. Jpn Acad. Ser. B Phys. Biol. Sci. 84, 246–263 (2008).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nowak, M., Chuchra, P. & Paprocka, J. Nonketotic hyperglycinemia: insight into current therapies. J. Clin. Med. 11, 3027 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

McBride, M. J. et al. Glycine homeostasis requires reverse SHMT flux. Cell Metab. 36, 103–115 (2024).

Article  CAS  PubMed  Google Scholar 

Solans, A., Estivill, X. & de la Luna, S. Cloning and characterization of human FTCD on 21q22.3, a candidate gene for glutamate formiminotransferase deficiency. Cytogenet. Cell Genet. 88, 43–49 (2000).

Article  CAS  PubMed  Google Scholar 

Mao, Y. et al. Structure of the bifunctional and Golgi-associated formiminotransferase cyclodeaminase octamer. EMBO J. 23, 2963–2971 (2004).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Newman, A. C. et al. Immune-regulated IDO1-dependent tryptophan metabolism is source of one-carbon units for pancreatic cancer and stellate cells. Mol. Cell 81, 2290–2302 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sen, K. & Hackett, J. C. Peroxo-iron mediated deformylation in sterol 14α-demethylase catalysis. J. Am. Chem. Soc. 132, 10293–10305 (2010).

Article  CAS  PubMed  Google Scholar 

Dorokhov, Y. L., Shindyapina, A. V., Sheshukova, E. V. & Komarova, T. V. Metabolic methanol: molecular pathways and physiological roles. Physiol. Rev. 95, 603–644 (2015).

Article  CAS  PubMed  Google Scholar 

Burgos-Barragan, G. et al. Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism. Nature 548, 549–554 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ternes, D. et al. The gut microbial metabolite formate exacerbates colorectal cancer progression. Nat. Metab. 4, 458–475 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ergal, I. et al. Formate utilization by the crenarchaeon desulfurococcus amylolyticus. Microorganisms 8, 454 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Laverde Gomez, J. A. et al. Formate cross-feeding and cooperative metabolic interactions revealed by transcriptomics in co-cultures of acetogenic and amylolytic human colonic bacteria. Environ. Microbiol. 21, 259–271 (2019).

Article  CAS  PubMed  Google Scholar 

Hughes, E. R. et al. Microbial respiration and formate oxidation as metabolic signatures of inflammation-associated dysbiosis. Cell Host Microbe 21, 208–219 (2017).

Article 

Comments (0)

No login
gif