Broad Institute, Cambridge, MA 02142, USA.
Science. 2012 May 25;336(6084):1040-4. doi: 10.1126/science.1218595.
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.
代谢重编程被认为是癌症的一个标志，但目前还缺乏对转化细胞中活跃的代谢途径进行系统表征。我们使用质谱法测量了 NCI-60 癌细胞系培养基中 219 种代谢物的消耗和释放（CORE）谱，并将这些数据与之前存在的基因表达图谱进行了整合。这项分析确定了甘氨酸的消耗以及线粒体甘氨酸生物合成途径的表达与癌细胞的增殖速度呈强相关性。抑制甘氨酸的摄取及其线粒体生物合成，优先损害快速增殖的细胞。此外，该途径的高表达与乳腺癌患者更高的死亡率相关。增加对甘氨酸的依赖可能代表了选择性靶向快速癌细胞增殖的代谢脆弱性。
