Metabolite Profiling Identifies a Key Role for Glycine in Rapid Cancer Cell Proliferation
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 th...
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Published in | Science (American Association for the Advancement of Science) Vol. 336; no. 6084; pp. 1040 - 1044 |
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Main Authors | , , , , , , , , , |
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 | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | These authors contributed equally to this work. |
ISSN: | 0036-8075 1095-9203 1095-9203 |
DOI: | 10.1126/science.1218595 |