Oncotarget

Research Perspectives:

Bioinformatics analysis of the serine and glycine pathway in cancer cells

Alexey Antonov _, Massimiliano Agostini, Maria Morello, Marilena Minieri, Gerry Melino, Ivano Amelio

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Oncotarget. 2014; 5:11004-11013. https://doi.org/10.18632/oncotarget.2668

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Abstract

Alexey Antonov1,*, Massimiliano Agostini1,2,*, Maria Morello2, Marilena Minieri2, Gerry Melino1,2,3, Ivano Amelio1

1Medical Research Council, Toxicology Unit, Leicester University, Leicester LE1 9HN, UK

2Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata”, Rome 00133, Italy

3Biochemistry Laboratory IDI-IRCC, University of Rome “Tor Vergata”, Rome 00133, Italy

*These authors contributed equally to this work

Correspondence to:

Massimiliano Agostini, e-mail: ma285@le.ac.uk

Alexey Antonov, e-mail: aa668@le.ac.uk

Keywords: Cancer Metabolism, Serine, Glycine, survival analysis

Received: October 27, 2014     Accepted: October 28, 2014     Published: November 21, 2014

ABSTRACT

Serine and glycine are amino acids that provide the essential precursors for the synthesis of proteins, nucleic acids and lipids. Employing 3 subsequent enzymes, phosphoglycerate dehydrogenase (PHGDH), phosphoserine phosphatase (PSPH), phosphoserine aminotransferase 1 (PSAT1), 3-phosphoglycerate from glycolysis can be converted in serine, which in turn can by converted in glycine by serine methyl transferase (SHMT). Besides proving precursors for macromolecules, serine/glycine biosynthesis is also required for the maintenance of cellular redox state. Therefore, this metabolic pathway has a pivotal role in proliferating cells, including cancer cells. In the last few years an emerging literature provides genetic and functional evidences that hyperactivation of serine/glycine biosynthetic pathway drives tumorigenesis. Here, we extend these observations performing a bioinformatics analysis using public cancer datasets. Our analysis highlighted the relevance of PHGDH and SHMT2 expression as prognostic factor for breast cancer, revealing a substantial ability of these enzymes to predict patient survival outcome. However analyzing patient datasets of lung cancer our analysis reveled that some other enzymes of the pathways, rather than PHGDH, might be associated to prognosis. Although these observations require further investigations they might suggest a selective requirement of some enzymes in specific cancer types, recommending more cautions in the development of novel translational opportunities and biomarker identification of human cancers.


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