Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation (Science, 2012, 336:1040-1044)

報告日期: 2012/10/19
報告時間: 15:10/16:00
報告學生: 蕭尊先
講評老師: 賴明德
附件下載: 下載[1232-1348725610-1.pdf] 

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

Mohit Jain, Roland Nilsson, Sonia Sharma, Nikhil Madhusudhan, Toshimori Kitami, Amanda L. Souza, Ran Kafri, Marc W. Kirschner, Clary B. Clish, and Vamsi K. Mootha

Science. 336:1040-4. 2012.

Student: Tsun-Hsien Hsiao                                   Place: Room 601

Commentator: Dr. Ming-Derg Lai                  Time: 2012/10/19 15:10~16:00

Abstract

  Metabolic reprogramming has been suggested as an emerging feature of cancer cells. Currently, the systematic analyze of metabolites profile in various cancer cell lines is lacking. In this study, the authors performed a consumption and release (CORE) profile of 219 metabolites in cultured medium of 60 well-characterized primary human cancer cell lines (NCI-60) using LC-MS/MS. Among all metabolites, they identified that glycine was highly consumed in rapidly proliferating transformed cell lines. The authors also evaluated the gene expression level of metabolic enzymes in the previous generated microarray of NCI-60 cell lines and found that mitochondrial glycine metabolic enzymes including serine hydroxymethyltransferase 2 (SHMT2), methylenetetrahydrofolate dehydrogenase 2/ cyclohydrolase (MTHFD2) and methylenetetrahydrofolate dehydrogenase 1-like/ formyltetrahydrofolate synthetase (MTHFD1L) were highly expressed in rapidly proliferating cancer cells. Knocking down SHMT2 and deprivation of glycine in cultured medium impaired the growth of rapidly proliferating LOX IMVI melanoma but not slowly proliferating A498 renal carcinoma. Metabolic tracing with 13C-glycine had revealed that the consumed glycine was used for de novo purine synthesis in cancer cells with short doubling time. Furthermore, the more active mitochondrial glycine synthesis pathway was related to greater mortality in breast cancer patients. In summary, using CORE profile, glycine had been identified as key metabolite in rapidly proliferating cancer cell lines and might be a target for cancer therapy.

 

Reference

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