Transformation by different oncogenes relies on specific metabolic adaptations. Issue 19 (1st October 2016)

• Record Type: Journal Article
• Authors: Peruzzo, Paolo; Comelli, Marina; Di Giorgio, Eros; Franforte, Elisa; Mavelli, Irene; Brancolini, Claudio
• Is Part Of: Cell cycle. Volume 15:Issue 19(2016)
• Page Start: 2656
• Page End: 2668
• Publication Date: 2016-10-01
• Subjects: class IIa -- CLN3 -- CPT1A -- ENO2 -- GLA -- Glycolysis -- HDAC4 -- HDAC5 -- HDAC7 -- HDAC9 -- HK2 -- MEF2A -- MEF2B -- MEF2C -- MEF2D -- mitochondria -- NSDHL -- OXPHOS -- PGK1 -- PKM2 -- RHOB -- Warburg; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2016.1215387
• Languages: English
• ISSNs: 1538-4101

Abstract

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.