Cancer cells use different metabolic pathways to their normal counterparts; this metabolic switch is necessary to support their rapid proliferation in oxygen- and nutrient-poor conditions. Mootha and colleagues perform metabolic profiling of the NCI-60 cancer cell line collection and report a key role for glycine in supporting rapid cellular proliferation (Science 336, 1040–1044; 2012).

The authors created metabolic consumption and release (CORE) profiles of the individual cancer cell lines to identify metabolites that are taken up or released. Correlating the CORE profiles with known cell proliferation rates revealed that glycine was generally consumed by highly proliferative cancer cells and released by slowly proliferating cells. Tracing radiolabelled glycine in a rapidly proliferating cell line revealed that it was used in de novo purine nucleotide synthesis.

Intriguingly, non-transformed, yet highly proliferative, cells also consumed glycine, suggesting that this amino acid supports rapid proliferation. Indeed, depleting extracellular glycine or knocking down the glycine-synthesizing enzyme SHMT2 blocked rapid proliferation by prolonging the G1 phase of the cell cycle. Glycine depletion did not affect slowly proliferating cells. Expression analyses of genes encoding mitochondrial glycine synthesis enzymes revealed that upregulation of these genes correlated with greater mortality and worse prognosis in breast cancer. Thus, the glycine synthesis pathway represents an attractive target for the development of anti-cancer therapeutics.