Publication Date:
2012-05-26
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526189/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526189/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jain, Mohit -- Nilsson, Roland -- Sharma, Sonia -- Madhusudhan, Nikhil -- Kitami, Toshimori -- Souza, Amanda L -- Kafri, Ran -- Kirschner, Marc W -- Clish, Clary B -- Mootha, Vamsi K -- K08 HL107451/HL/NHLBI NIH HHS/ -- K08HL107451/HL/NHLBI NIH HHS/ -- R01 DK081457/DK/NIDDK NIH HHS/ -- R01 GM026875/GM/NIGMS NIH HHS/ -- R01DK081457/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2012 May 25;336(6084):1040-4. doi: 10.1126/science.1218595.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22628656" target="_blank"〉PubMed〈/a〉
Keywords:
Breast Neoplasms/genetics/metabolism/pathology
;
Cell Cycle
;
Cell Line
;
Cell Line, Tumor
;
*Cell Proliferation
;
Cell Transformation, Neoplastic
;
Chromatography, Liquid
;
Culture Media
;
Gene Expression
;
Gene Expression Profiling
;
Glycine/biosynthesis/*metabolism
;
Humans
;
Metabolic Networks and Pathways/genetics
;
Metabolome
;
Mitochondria/enzymology/metabolism
;
Neoplasms/genetics/*metabolism/*pathology
;
Purines/biosynthesis
;
Tandem Mass Spectrometry
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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