Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression
Arun Sreekumar,Laila M. Poisson,Thekkelnaycke M. Rajendiran,Amjad Khan,Qi Cao,Jindan Yu,Bharathi Laxman,Rohit Mehra,Robert J. Lonigro,Yong Li,Mukesh K. Nyati,Aarif Ahsan,Shanker Kalyana-Sundaram,Bo Han,Xuhong Cao,Jaeman Byun,Gilbert S. Omenn,Debashis Ghosh,Subramaniam Pennathur,Danny C. Alexander,Alvin Berger,Jeffrey R. Shuster,John T. Wei,Sooryanarayana Varambally,Christopher A. Beecher,Arul M. Chinnaiyan +25 more
TLDR
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.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.read more
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HMDB 3.0—The Human Metabolome Database in 2013
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TL;DR: New database visualization tools and new data content have been added or enhanced to the HMDB, which includes better spectral viewing tools, more powerful chemical substructure searches, an improved chemical taxonomy and better, more interactive pathway maps.
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MassBank: a public repository for sharing mass spectral data for life sciences.
Hisayuki Horai,Masanori Arita,Masanori Arita,Shigehiko Kanaya,Yoshito Nihei,Tasuku Ikeda,Kazuhiro Suwa,Yuya Ojima,Kenichi Tanaka,Satoshi Tanaka,Ken Aoshima,Yoshiya Oda,Yuji Kakazu,Miyako Kusano,Takayuki Tohge,Fumio Matsuda,Yuji Sawada,Masami Yokota Hirai,Hiroki Nakanishi,Kazutaka Ikeda,Naoshige Akimoto,Takashi Maoka,Hiroki Takahashi,Takeshi Ara,Nozomu Sakurai,Hideyuki Suzuki,Daisuke Shibata,Steffen Neumann,Takashi Iida,Ken Tanaka,Kimito Funatsu,Fumito Matsuura,Tomoyoshi Soga,Ryo Taguchi,Kazuki Saito,Takaaki Nishioka +35 more
TL;DR: MassBank is the first public repository of mass spectra of small chemical compounds for life sciences and provides a merged spectrum for each compound prepared by merging the analyzed ESI-MS(2) data on an identical compound under different collision-induced dissociation conditions.
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TL;DR: Because of the inherent sensitivity of metabolomics, subtle alterations in biological pathways can be detected to provide insight into the mechanisms that underlie various physiological conditions and aberrant processes, including diseases.
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Metabolite Profiling Identifies a Key Role for Glycine in Rapid Cancer Cell Proliferation
Mohit Jain,Roland Nilsson,Sonia Sharma,Nikhil Madhusudhan,Nikhil Madhusudhan,Toshimori Kitami,Toshimori Kitami,Amanda Souza,Ran Kafri,Marc W. Kirschner,Clary B. Clish,Vamsi K. Mootha,Vamsi K. Mootha +12 more
TL;DR: Glycine consumption and expression of the mitochondrial glycine biosynthetic pathway was identified as strongly correlated with rates of proliferation across cancer cells, and higher expression of this pathway was associated with greater mortality in breast cancer patients.
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