Metabolic reprogramming is a hallmark of transformed cells, but knowledge of the specific pathways that are altered in cancer is still limited. To identify metabolic pathways commonly altered in multiple cancers, Jain, Nilsson et al. applied consumption and release (CORE) profiling to the NCI-60 cell lines (60 primary human cancer cell lines from nine tumour types). This led to the identification of glycine – a non-essential amino acid – as a metabolite that is consumed by rapidly growing cancer cells and released by slow-growing cancer cells. Glycine is endogenously produced in both the cytosol and mitochondria; using genetic profiling, the authors determined that transformed cells have an increased reliance on either exogenous glycine or glycine produced by the mitochondrial pathway. Analysis of existing transcriptome datasets from six independent cohorts of early-stage breast cancer patients showed that increased expression of genes associated with the mitochondrial glycine biosynthesis pathway is associated with increased mortality. Thus, glycine metabolism might be a promising therapeutic target in breast and possibly other types of cancer.

JainM., NilssonR., SharmaS., MadhusudhanN., KitamiT., SouzaA. L., KafriR., KirschnerM. W., ClishC. B., MoothaV. K. (2012). Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science336, 10401044.

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