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PMID: 22628656 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation.

Science (New York, N.Y.) ·Vol. 336 ·No. 6084 ·2012-05-25 ·Pages 1040-4

Jain M, Nilsson R, Sharma S, Madhusudhan N, Kitami T, Souza AL, Kafri R, Kirschner MW, Clish CB, Mootha VK

Abstract

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.

MeSH Terms
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
Chemicals
Culture Media Purines Glycine
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Jain Mohit
Broad Institute, Cambridge, MA 02142, USA.
Nilsson Roland
Sharma Sonia
Madhusudhan Nikhil
Kitami Toshimori
Souza Amanda L
Kafri Ran
Kirschner Marc W
Clish Clary B
Mootha Vamsi K
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1218595
Published
2012-05-25
Pages
1040-4
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3526189
Subset
IM
Grants
NIGMS NIH HHS · R01 GM026875 · United States
NIEHS NIH HHS · R01 ES027595 · United States
NHLBI NIH HHS · K08HL107451 · United States
NHLBI NIH HHS · K08 HL107451 · United States
NIDDK NIH HHS · R01 DK081457 · United States
NIDDK NIH HHS · R01DK081457 · United States
Corrections
CommentIn
PMID: 22628644
CommentIn
PMID: 22688577
External Links
PubMed source DOI: 10.1126/science.1218595 PMC Full Text View journal details
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