Peruzzo 2016 Cell Cycle
|Peruzzo P, Comelli M, Di Giorgio E, Franforte E, Mavelli I, Brancolini C (2016) Transformation by different oncogenes relies on specific metabolic adaptations. Cell Cycle 15:2656-68.|
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.
• Keywords: CLN3, CPT1A, ENO2, GLA, Glycolysis, HDAC4, HDAC5, HDAC7, HDAC9, HK2, MEF2A, MEF2B, MEF2C, MEF2D, NSDHL, OXPHOS, PGK1, PKM2, RHOB, Warburg, class IIa, Mitochondria, NIH 3T3 cells
Labels: MiParea: Respiration, nDNA;cell genetics, Genetic knockout;overexpression Pathology: Cancer
Organism: Mouse Tissue;cell: Fibroblast Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ET Pathway: ROX HRR: Oxygraph-2k