title: Transformation by different oncogenes relies on specific metabolic adaptations.
abstract: Metabolic adaptations are emerging as common traits of cancer cells and tumor progression. In vitro transformation of NIH 3T3 cells allows the analysis of the metabolic changes triggered by a single oncogene. In this work, we have compared the metabolic changes induced by H-RAS and by the nuclear resident mutant of histone deacetylase 4 (HDAC4). RAS-transformed cells exhibit a dominant aerobic glycolytic phenotype characterized by up-regulation of glycolytic enzymes, reduced oxygen consumption and a defect in complex I activity. In this model of transformation, glycolysis is strictly required for sustaining the ATP levels and the robust cellular proliferation. By contrast, in HDAC4/TM transformed cells, glycolysis is only modestly up-regulated, lactate secretion is not augmented and, instead, mitochondrial oxygen consumption is increased. Our results demonstrate that cellular transformation can be accomplished through different metabolic adaptations and HDAC4/TM cells can represent a useful model to investigate oncogene-driven metabolic changes besides the Warburg effect.
authors.affiliation: a Department of Medical and Biological Sciences , Università degli Studi di Udine , Udine Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Peruzzo
authors.affiliation: a Department of Medical and Biological Sciences , Università degli Studi di Udine , Udine Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Comelli
authors.affiliation: a Department of Medical and Biological Sciences , Università degli Studi di Udine , Udine Italy.
authors.forename: Eros
authors.initials: E
authors.lastname: Di Giorgio
authors.affiliation: a Department of Medical and Biological Sciences , Università degli Studi di Udine , Udine Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Franforte
authors.affiliation: a Department of Medical and Biological Sciences , Università degli Studi di Udine , Udine Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Mavelli
authors.affiliation: a Department of Medical and Biological Sciences , Università degli Studi di Udine , Udine Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Brancolini
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics; D019069:Cell Respiration; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006019:Glycolysis; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D041681:NIH 3T3 Cells; D009857:Oncogenes; D018631:ras Proteins / Q000378:metabolism
chemical_list: D019344:Lactic Acid; D006655:Histone Deacetylases; D018631:ras Proteins; D042967:Electron Transport Complex I
keywords: CLN3; CPT1A; ENO2; GLA; Glycolysis; HDAC4; HDAC5; HDAC7; HDAC9; HK2; MEF2A; MEF2B; MEF2C; MEF2D; NSDHL; OXPHOS; PGK1; PKM2; RHOB; Warburg; class IIa; mitochondria