Metabolomic Profiles Delineate Potential Role for Sarcosine in Prostate Cancer Progression

By A. Sreekumar, L. Poisson, Thekkelnaycke M. Rajendiran, Amjad P. Khan, Q. Cao, Jindan Yu, B. Laxman, R. Mehra, R. Lonigro, Yong Li and 16 more. Nature, 2009

2,206 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Spectroscopy

View Paper: https://www.semanticscholar.org/paper/03c46e61a60c4b7c07c4ff59218d18a8f7654613

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Citations in the corpus

An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma (2016, positive): “In addition to targeted approaches, global metabolomic profiling has been performed on a comparatively smaller number of cancer types, including prostate, breast, brain, liver, and kidney cancers, at modest scale (n% 65) (Budhu et al., 2013; Huang et al., 2013; Jaramillo and Zhang, 2013; Prabhu et a”
An atlas of genetic influences on human blood metabolites (2014, background): “58 Pantothenate and CoA (1) 56 Hemoglobin and porphyrin (5) 55 Tocopherol (2) 53 Fibrinogen cleavage peptide (3) 52 Dipeptide (9) 49 Polyamine metabolism (1) 48 Amino fatty acid (1) 47 Guanidino and acetamido (1) 45 Tryptophan (10) 44 Glutathione (2) 42 Branched-chain amino acid (14) 41 Butanoate (3”
Metabolomics for Investigating Physiological and Pathophysiological Processes. (2019, methodology): “Over the past decade more than a half dozen additional oncometabolites have been discovered including L-2-hydroxyglutarate (430), cystathionine (422), hypotaurine (160), sarcosine (439), and several secondary bile acids (145).”
MassBank: a public repository for sharing mass spectral data for life sciences. (2010, background): “Because this limited availability restricts the ratio of identified metabolites to those detected on LC-MS and -MS2, it remains as low as 3–5% (48/1233) in plant[12] and 20–30% (175/626) in human tissues.[13] Usually, metabolites are identified by comparing two data, retention index of chromatograph”
Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate (2012, background): “Additional proposed functions include the generation of precursors for pyrimidine synthesis and the production of sarcosine, a glycine-derived metabolite linked to prostate cancer progression (Sreekumar et al., 2009; Zhang et al., 2012).”
One-Carbon Metabolism in Health and Disease. (2017, background): “Sarcosine levels are elevated in aggressive and metastatic prostate cancer tumors (Sreekumar et al., 2009).”
Analytical Methods in Untargeted Metabolomics: State of the Art in 2015 (2015, positive): “HCA is also a powerful clustering and visualization tool that provides a clustering procedure at the feature and sample levels according to a predefined distance measure (Brauer et al., 2006; Sreekumar et al., 2009).”