title: Bioinformatics analysis of the serine and glycine pathway in cancer cells.
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.
authors.affiliation: Medical Research Council, Toxicology Unit, Leicester University, Leicester LE1 9HN, UK.
authors.forename: Alexey
authors.initials: A
authors.lastname: Antonov
authors.affiliation: Medical Research Council, Toxicology Unit, Leicester University, Leicester LE1 9HN, UK. Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome 00133, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Agostini
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome 00133, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Morello
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome 00133, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Minieri
authors.affiliation: Medical Research Council, Toxicology Unit, Leicester University, Leicester LE1 9HN, UK. Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome 00133, Italy. Biochemistry Laboratory IDI-IRCC, University of Rome "Tor Vergata", Rome 00133, Italy.
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
authors.affiliation: Medical Research Council, Toxicology Unit, Leicester University, Leicester LE1 9HN, UK.
authors.forename: Ivano
authors.initials: I
authors.lastname: Amelio
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods; D023281:Genomics; D005998:Glycine / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D012694:Serine; D005998:Glycine