期刊
NEOPLASIA
卷 15, 期 5, 页码 491-+出版社
ELSEVIER SCIENCE INC
DOI: 10.1593/neo.13314
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资金
- Early Detection Research Network [UO1 CA111275]
- Prostate Cancer Specialized Program of Research Excellence [P50CA69568]
- National Institutes of Health [R01CA132874, RO1CA133458, RO3CA139489, UO1CA167234, R01CA13345]
- Department of Defense [W81XWH-12-1-0130]
- Doris Duke Charitable Foundation Clinical Scientist Award
- Prostate Cancer Foundation
- Howard Hughes Medical Institute
- Direct For Mathematical & Physical Scien
- Division Of Mathematical Sciences [1545277] Funding Source: National Science Foundation
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.
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