Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression
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- 1 February 2009
- journal article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 457 (7231), 910-914
- https://doi.org/10.1038/nature07762
Abstract
Multiple, complex molecular events characterize cancer development and progression. Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of critical biomarkers for cancer invasion and disease aggressiveness. Although gene and protein expression have been extensively profiled in human tumours, little is known about the global metabolomic alterations that characterize neoplastic progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we profiled more than 1,126 metabolites across 262 clinical samples related to prostate cancer (42 tissues and 110 each of urine and plasma). These unbiased metabolomic profiles were able to distinguish benign prostate, clinically localized prostate cancer and metastatic disease. Sarcosine, an N-methyl derivative of the amino acid glycine, was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non-invasively in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells. Knockdown of glycine-N-methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Addition of exogenous sarcosine or knockdown of the enzyme that leads to sarcosine degradation, sarcosine dehydrogenase, induced an invasive phenotype in benign prostate epithelial cells. Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway. Here, by profiling the metabolomic alterations of prostate cancer progression, we reveal sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity.Keywords
This publication has 18 references indexed in Scilit:
- Genomic Loss of microRNA-101 Leads to Overexpression of Histone Methyltransferase EZH2 in CancerScience, 2008
- A Polycomb Repression Signature in Metastatic Prostate Cancer Predicts Cancer OutcomeCancer Research, 2007
- Integrative Genomics Analysis Reveals Silencing of β-Adrenergic Signaling by Polycomb in Prostate CancerCancer Cell, 2007
- Integrative molecular concept modeling of prostate cancer progressionNature Genetics, 2006
- Recurrent Fusion of TMPRSS2 and ETS Transcription Factor Genes in Prostate CancerScience, 2005
- EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cellsProceedings of the National Academy of Sciences of the United States of America, 2003
- Role of Histone H3 Lysine 27 Methylation in Polycomb-Group SilencingScience, 2002
- The polycomb group protein EZH2 is involved in progression of prostate cancerNature, 2002
- A Direct Approach to False Discovery RatesJournal of the Royal Statistical Society Series B: Statistical Methodology, 2002
- [12] DNA arrays for analysis of gene expressionMethods in Enzymology, 1999