Mapping Metabolic Events in the Cancer Cell Cycle Reveals Arginine Catabolism in the Committed SG₂M Phase.

ABSTRACT: Alterations in cell-cycle regulation and cellular metabolism are associated with cancer transformation, and enzymes active in the committed cell-cycle phase may represent vulnerabilities of cancer cells. Here, we map metabolic events in the G₁ and SG₂M phases by combining cell sorting with mass spectrometry-based isotope tracing, revealing hundreds of cell-cycle-associated metabolites. In particular, arginine uptake and ornithine synthesis are active during SG₂M in transformed but not in normal cells, with the mitochondrial arginase 2 (ARG2) enzyme as a potential mechanism. While cancer cells exclusively use ARG2, normal epithelial cells synthesize ornithine via ornithine aminotransferase (OAT). Knockdown of ARG2 markedly reduces cancer cell growth and caus

SUBMITTER: Roci I 

PROVIDER: S-EPMC6663478 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature