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The role of sarcosine metabolism in prostate cancer progression.

The role of sarcosine metabolism in prostate cancer progression.

Authors :
Khan AP
Rajendiran TM
Ateeq B
Asangani IA
Athanikar JN
Yocum AK
Mehra R
Siddiqui J
Palapattu G
Wei JT
Michailidis G
Sreekumar A
Chinnaiyan AM
Source :
Neoplasia (New York, N.Y.) [Neoplasia] 2013 May; Vol. 15 (5), pp. 491-501.
Publication Year :
2013

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.

Details

Language :
English
ISSN :
1476-5586
Volume :
15
Issue :
5
Database :
MEDLINE
Journal :
Neoplasia (New York, N.Y.)
Publication Type :
Academic Journal
Accession number :
23633921
Full Text :
https://doi.org/10.1593/neo.13314