title: The role of sarcosine metabolism in prostate cancer progression.
abstract: Metabolomic profiling of prostate cancer (PCa) progression identified markedly elevated levels of sarcosine (N-methyl glycine) in metastatic PCa and modest but significant elevation of the metabolite in PCa urine. Here, we examine the role of key enzymes associated with sarcosine metabolism in PCa progression. Consistent with our earlier report, sarcosine levels were significantly elevated in PCa urine sediments compared to controls, with a modest area under the receiver operating characteristic curve of 0.71. In addition, the expression of sarcosine biosynthetic enzyme, glycine N-methyltransferase (GNMT), was elevated in PCa tissues, while sarcosine dehydrogenase (SARDH) and pipecolic acid oxidase (PIPOX), which metabolize sarcosine, were reduced in prostate tumors. Consistent with this, GNMT promoted the oncogenic potential of prostate cells by facilitating sarcosine production, while SARDH and PIPOX reduced the oncogenic potential of prostate cells by metabolizing sarcosine. Accordingly, addition of sarcosine, but not glycine or alanine, induced invasion and intravasation in an in vivo PCa model. In contrast, GNMT knockdown or SARDH overexpression in PCa xenografts inhibited tumor growth. Taken together, these studies substantiate the role of sarcosine in PCa progression.
authors: Michigan Center for Translational Pathology, Ann Arbor, MI, USA.
authors: Amjad P
authors: AP
authors: Khan
authors: Thekkelnaycke M
authors: TM
authors: Rajendiran
authors: Bushra
authors: B
authors: Ateeq
authors: Irfan A
authors: IA
authors: Asangani
authors: Jyoti N
authors: JN
authors: Athanikar
authors: Anastasia K
authors: AK
authors: Yocum
authors: Rohit
authors: R
authors: Mehra
authors: Javed
authors: J
authors: Siddiqui
authors: Ganesh
authors: G
authors: Palapattu
authors: John T
authors: JT
authors: Wei
authors: George
authors: G
authors: Michailidis
authors: Arun
authors: A
authors: Sreekumar
authors: Arul M
authors: AM
authors: Chinnaiyan
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D018450:Disease Progression; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D050938:Glycine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology / Q000652:urine*; D012521:Sarcosine / Q000652:urine*; D050892:Sarcosine Dehydrogenase / Q000235:genetics / Q000378:metabolism; D050879:Sarcosine Oxidase / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; C494349:PIPOX protein, human; D050879:Sarcosine Oxidase; C494395:SARDH protein, human; D050892:Sarcosine Dehydrogenase; C494510:GNMT protein, human; D050938:Glycine N-Methyltransferase; D012521:Sarcosine
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