Metabolite Profiling Identifies a Key Role for Glycine in Rapid Cancer Cell Proliferation

• Published in: Science (American Association for the Advancement of Science) Vol. 336; no. 6084; pp. 1040 - 1044
• Main Authors: Jain, Mohit, Nilsson, Roland, Sharma, Sonia, Madhusudhan, Nikhil, Kitami, Toshimori, Souza, Amanda L., Kafri, Ran, Kirschner, Marc W., Clish, Clary B., Mootha, Vamsi K.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 25.05.2012; The American Association for the Advancement of Science
• Subjects: Biological and medical sciences; Biosynthesis; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Carcinogenesis, carcinogens and anticarcinogens; Cell adhesion & migration; Cell Cycle; Cell growth; Cell Line; Cell Line, Tumor; Cell lines; Cell Proliferation; Cell Transformation, Neoplastic; Cellular metabolism; Chromatography, Liquid; Culture Media; Enzymes; Gene Expression; Gene Expression Profiling; General aspects; Glycine - biosynthesis; Glycine - metabolism; Humans; Mass spectrometry; Medical sciences; Medicin och hälsovetenskap; Metabolic Networks and Pathways - genetics; Metabolites; Metabolome; Mitochondria; Mitochondria - enzymology; Mitochondria - metabolism; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Purines; Purines - biosynthesis; Stem cells; Tandem Mass Spectrometry; Transformed cell line; Tumor cell line; Tumors; Human; Cell proliferation; Cancerology; Metabolite; Aminoacid; Established cell line; Malignant tumor; Glycine; Carcinogenesis; Cancer
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1218595

Metabolic reprogramming has been proposed to be a hallmark of cancer, yet a systematic characterization of the metabolic pathways active in transformed cells is currently lacking. Using mass spectrometry, we measured the consumption and release (CORE) profiles of 219 metabolites from media across the NCI-60 cancer cell lines, and integrated these data with a preexisting atlas of gene expression. This analysis identified glycine consumption and expression of the mitochondrial glycine biosynthetic pathway as strongly correlated with rates of proliferation across cancer cells. Antagonizing glycine uptake and its mitochondrial biosynthesis preferentially impaired rapidly proliferating cells. Moreover, higher expression of this pathway was associated with greater mortality in breast cancer patients. Increased reliance on glycine may represent a metabolic vulnerability for selectively targeting rapid cancer cell proliferation.