The role of B₁₂ deficiency and methionine synthase in methionine-dependent cancer cells.

ABSTRACT:

Background

Human cells can synthesize methionine from homocysteine and folate-coupled methyl groups via the B₁₂-dependent enzyme methionine synthase (MTR). Yet, it has been known for decades that cancer cells fail to grow when methionine is replaced by homocysteine, a phenomenon known as methionine dependence. The underlying mechanism remains unknown.

Methods

Cancer cell lines were cultured with homocysteine in place of methionine, and growth responses were measured. Revertant cells capable of growing in homocysteine were generated through long-term culture with high B₁₂ and analyzed using single-cell RNA-seq. Metabolite uptake/release was measured using isotope dilution and MTR activity was assessed using metabolic flux analysis (MFA). Functional rescu

SUBMITTER: Husseiny MMAE 

PROVIDER: S-EPMC12220533 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature