4.8 Article

Methionine synthase supports tumour tetrahydrofolate pools

期刊

NATURE METABOLISM
卷 3, 期 11, 页码 1512-+

出版社

NATURE PORTFOLIO
DOI: 10.1038/s42255-021-00465-w

关键词

-

资金

  1. NCI NIH HHS [R01 CA163591] Funding Source: Medline
  2. NIDDK NIH HHS [DP1 DK113643] Funding Source: Medline

向作者/读者索取更多资源

The research demonstrates that methionine synthase plays a crucial role not only in synthesizing methionine but also in preventing folate trapping and converting 5-methyl-THF into other folate species.
Ghergurovich, Xu and Wang et al. show that methionine synthase is important for tumour cell survival through the generation of tetrahydrofolate rather than methionine. 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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据