Methionine synthase is essential for cancer cell proliferation in physiological folate environments.
Nat Metab
; 3(11): 1500-1511, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34799701
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase
/
Neoplasias
Tipo de estudo:
Etiology_studies
Limite:
Humans
Idioma:
En
Revista:
Nat Metab
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos