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

Science
Authors
Keywords
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.

Year of Publication
2012
Journal
Science
Volume
336
Issue
6084
Pages
1040-4
Date Published
2012 May 25
ISSN
1095-9203
URL
DOI
10.1126/science.1218595
PubMed ID
22628656
PubMed Central ID
PMC3526189
Links
Grant list
R01 GM026875 / GM / NIGMS NIH HHS / United States
K08HL107451 / HL / NHLBI NIH HHS / United States
K08 HL107451 / HL / NHLBI NIH HHS / United States
R01 DK081457 / DK / NIDDK NIH HHS / United States
R01DK081457 / DK / NIDDK NIH HHS / United States