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

被引：1116

作者：

Jain, Mohit ^{[1
,2
,3
,4
,5
]}

Nilsson, Roland ^{[1
,2
,3
,4
,6
]}

Sharma, Sonia ^{[7
]}

Madhusudhan, Nikhil ^{[1
,2
,3
,4
]}

Kitami, Toshimori ^{[1
,2
,3
,4
]}

Souza, Amanda L. ^{[1
]}

Kafri, Ran ^{[2
]}

Kirschner, Marc W. ^{[2
]}

Clish, Clary B. ^{[1
]}

Mootha, Vamsi K. ^{[1
,2
,3
,4
]}

机构：

[1] Broad Inst, Cambridge, MA 02142 USA

[2] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA

[3] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[5] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA

[6] Karolinska Inst, Dept Med, Unit Computat Med, S-17176 Stockholm, Sweden

[7] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA

来源：

SCIENCE | 2012年 / 336卷 / 6084期

关键词：

SERINE HYDROXYMETHYLTRANSFERASE; EXPRESSION SIGNATURE; DEPENDENCE; PATHWAY; SCREEN;

D O I：

10.1126/science.1218595

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1040 / 1044

页数：5

共 29 条

[1] High-throughput classification of yeast mutants for functional genomics using metabolic footprinting [J].