Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression
dc.contributor.author | Sreekumar, Arun | en_US |
dc.contributor.author | Poisson, Laila M. | en_US |
dc.contributor.author | Rajendiran, Thekkelnaycke M. | en_US |
dc.contributor.author | Khan, Amjad P. | en_US |
dc.contributor.author | Cao, Qi | en_US |
dc.contributor.author | Yu, Jindan | en_US |
dc.contributor.author | Laxman, Bharathi | en_US |
dc.contributor.author | Mehra, Rohit | en_US |
dc.contributor.author | Lonigro, Robert J. | en_US |
dc.contributor.author | Li, Yong | en_US |
dc.contributor.author | Nyati, Mukesh K. | en_US |
dc.contributor.author | Ahsan, Aarif | en_US |
dc.contributor.author | Kalyana-Sundaram, Shanker | en_US |
dc.contributor.author | Han, Bo | en_US |
dc.contributor.author | Cao, Xuhong | en_US |
dc.contributor.author | Byun, Jaeman | en_US |
dc.contributor.author | Omenn, Gilbert S. | en_US |
dc.contributor.author | Ghosh, Debashis | en_US |
dc.contributor.author | Pennathur, Subramaniam | en_US |
dc.contributor.author | Alexander, Danny C. | en_US |
dc.contributor.author | Berger, Alvin | en_US |
dc.contributor.author | Shuster, Jeffrey R. | en_US |
dc.contributor.author | Wei, John T. | en_US |
dc.contributor.author | Varambally, Sooryanarayana | en_US |
dc.contributor.author | Beecher, Christopher A. | en_US |
dc.contributor.author | Chinnaiyan, Arul M. | en_US |
dc.date.accessioned | 2009-06-01T17:29:47Z | |
dc.date.available | 2009-06-01T17:29:47Z | |
dc.date.issued | 2008-02-11 | en_US |
dc.identifier.citation | Sreekumar, Arun; Poisson, Laila M.; Rajendiran, Thekkelnaycke M.; Khan, Amjad P.; Cao, Qi; Yu, Jindan; Laxman, Bharathi; Mehra, Rohit; Lonigro, Robert J.; Li, Yong; Nyati, Mukesh K.; Ahsan, Aarif; Kalyana-Sundaram, Shanker; Han, Bo; Cao, Xuhong; Byun, Jaeman; Omenn, Gilbert S.; Ghosh, Debashis; Pennathur, Subramaniam; Alexander, Danny C.; Berger, Alvin; Shuster, Jeffrey R.; Wei, John T.; Varambally, Sooryanarayana; Beecher, Christopher; Chinnaiyan, Arul M.. (2008) "Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression." Nature 457(7231): 910-U176. <http://hdl.handle.net/2027.42/62661> | en_US |
dc.identifier.issn | 0028-0836 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/62661 | |
dc.description.abstract | Multiple, complex molecular events characterize cancer development and progression(1,2). 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. | en_US |
dc.description.sponsorship | Early Detection Research Network ; National Institutes of Health ; MTTC ; Clinical Translational Science Award ; Fund for Discovery of the University of Michigan Comprehensive Cancer Center ; University of Michigan Cancer Biostatistics Training Grant ; Doris Duke Charitable Foundation | en_US |
dc.description.sponsorship | We thank J. Granger for help in manuscript preparation, J. Siddiqui and R. Varambally for help with the clinical database, and A. Vellaichamy and S. Pullela for technical assistance. We thank K. Pienta for access to metastatic prostate cancer samples from the University of Michigan Prostate SPORE rapid autopsy programme. This work is supported in part by the Early Detection Research Network (A.M.C., J.T.W.), National Institutes of Health (A.S., S.P., J.B., T.M.R., D.G., G.S.O. and A.M.C.) and an MTTC grant (G.S.O. and A.S.). A.M.C. is supported by a Clinical Translational Science Award from the Burroughs Welcome Foundation. A. S. is supported by a grant from the Fund for Discovery of the University of Michigan Comprehensive Cancer Center. L. M. P. is supported by the University of Michigan Cancer Biostatistics Training Grant. A. M. C and S. P. are supported by the Doris Duke Charitable Foundation. | en_US |
dc.format.extent | 871993 bytes | |
dc.format.extent | 2489 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Nature Publishing Group | en_US |
dc.source | Nature | en_US |
dc.title | Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression | en_US |
dc.type | Article | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Ctr Computat Med & Biol, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | Ghosh, Debashis] Univ Michigan, Sch Med, Dept Biostat, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | Ahsan, Aarif] Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | Pennathur, Subramaniam] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | [Omenn, Gilbert S.] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | [Varambally, Sooryanarayana] Univ Michigan, Sch Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationother | [Sreekumar, Arun | en_US |
dc.contributor.affiliationother | Rajendiran, Thekkelnaycke M. | en_US |
dc.contributor.affiliationother | Khan, Amjad P. | en_US |
dc.contributor.affiliationother | Cao, Qi | en_US |
dc.contributor.affiliationother | Yu, Jindan | en_US |
dc.contributor.affiliationother | Laxman, Bharathi | en_US |
dc.contributor.affiliationother | Mehra, Rohit | en_US |
dc.contributor.affiliationother | Lonigro, Robert J. | en_US |
dc.contributor.affiliationother | Li, Yong | en_US |
dc.contributor.affiliationother | Kalyana-Sundaram, Shanker | en_US |
dc.contributor.affiliationother | Han, Bo | en_US |
dc.contributor.affiliationother | Cao, Xuhong | en_US |
dc.contributor.affiliationother | Varambally, Sooryanarayana | en_US |
dc.contributor.affiliationother | Beecher, Christopher | en_US |
dc.contributor.affiliationother | [Sreekumar, Arun | en_US |
dc.contributor.affiliationother | Omenn, Gilbert S. | en_US |
dc.contributor.affiliationother | Pennathur, Subramaniam | en_US |
dc.contributor.affiliationother | Beecher, Christopher | en_US |
dc.contributor.affiliationother | [Sreekumar, Arun | en_US |
dc.contributor.affiliationother | Rajendiran, Thekkelnaycke M. | en_US |
dc.contributor.affiliationother | Khan, Amjad P. | en_US |
dc.contributor.affiliationother | Cao, Qi | en_US |
dc.contributor.affiliationother | Yu, Jindan | en_US |
dc.contributor.affiliationother | Laxman, Bharathi | en_US |
dc.contributor.affiliationother | Mehra, Rohit | en_US |
dc.contributor.affiliationother | Li, Yong | en_US |
dc.contributor.affiliationother | Kalyana-Sundaram, Shanker | en_US |
dc.contributor.affiliationother | Han, Bo | en_US |
dc.contributor.affiliationother | Cao, Xuhong | en_US |
dc.contributor.affiliationother | Varambally, Sooryanarayana | en_US |
dc.contributor.affiliationother | Beecher, Christopher | en_US |
dc.contributor.affiliationother | [Sreekumar, Arun | en_US |
dc.contributor.affiliationother | Lonigro, Robert J. | en_US |
dc.contributor.affiliationother | Nyati, Mukesh K. | en_US |
dc.contributor.affiliationother | Ghosh, Debashis | en_US |
dc.contributor.affiliationother | Pennathur, Subramaniam | en_US |
dc.contributor.affiliationother | Wei, John T. | en_US |
dc.contributor.affiliationother | Varambally, Sooryanarayana | en_US |
dc.contributor.affiliationother | [Poisson, Laila M. | en_US |
dc.contributor.affiliationother | [Nyati, Mukesh K. | en_US |
dc.contributor.affiliationother | [Byun, Jaeman | en_US |
dc.contributor.affiliationother | Omenn, Gilbert S. | en_US |
dc.contributor.affiliationother | [Wei, John T. | en_US |
dc.contributor.affiliationother | [Ghosh, Debashis] Penn State Univ, Dept Stat, University Pk, PA 16802 USA | en_US |
dc.contributor.affiliationother | [Ghosh, Debashis] Penn State Univ, Huck Inst Life Sci, University Pk, PA 16802 USA | en_US |
dc.contributor.affiliationother | [Alexander, Danny C. | en_US |
dc.contributor.affiliationother | Berger, Alvin | en_US |
dc.contributor.affiliationother | Shuster, Jeffrey R.] Metabolon Inc, Durham, NC 27713 USA | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/62661/1/nature07762.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1038/nature07762 | en_US |
dc.identifier.source | Nature | en_US |
dc.contributor.authoremail | arul@umich.edu | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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