title: Peroxisome proliferator-activated receptor γ (PPARγ) mediates a Ski oncogene-induced shift from glycolysis to oxidative energy metabolism.
abstract: Overexpression of the Ski oncogene induces oncogenic transformation of chicken embryo fibroblasts (CEFs). However, unlike most other oncogene-transformed cells, Ski-transformed CEFs (Ski-CEFs) do not display the classical Warburg effect. On the contrary, Ski transformation reduced lactate production and glucose utilization in CEFs. Compared with CEFs, Ski-CEFs exhibited enhanced TCA cycle activity, fatty acid catabolism through β-oxidation, glutamate oxidation, oxygen consumption, as well as increased numbers and mass of mitochondria. Interestingly, expression of PPARγ, a key transcription factor that regulates adipogenesis and lipid metabolism, was dramatically elevated at both the mRNA and protein levels in Ski-CEFs. Accordingly, PPARγ target genes that are involved in lipid uptake, transport, and oxidation were also markedly up-regulated by Ski. Knocking down PPARγ in Ski-CEFs by RNA interference reversed the elevated expression of these PPARγ target genes, as well as the shift to oxidative metabolism and the increased mitochondrial biogenesis. Moreover, we found that Ski co-immunoprecipitates with PPARγ and co-activates PPARγ-driven transcription.
authors.affiliation: Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Ye
authors.forename: Hélène
authors.initials: H
authors.lastname: Lemieux
authors.forename: Charles L
authors.initials: CL
authors.lastname: Hoppel
authors.forename: Richard W
authors.initials: RW
authors.lastname: Hanson
authors.forename: Parvin
authors.initials: P
authors.lastname: Hakimi
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Croniger
authors.forename: Michelle
authors.initials: M
authors.lastname: Puchowicz
authors.forename: Vernon E
authors.initials: VE
authors.lastname: Anderson
authors.forename: Hisashi
authors.initials: H
authors.lastname: Fujioka
authors.forename: Ed
authors.initials: E
authors.lastname: Stavnezer
mesh_terms: D050156:Adipogenesis / Q000502:physiology; D000818:Animals; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006019:Glycolysis / Q000502:physiology*; D050356:Lipid Metabolism / Q000502:physiology; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000502:physiology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D047495:PPAR gamma; D011518:Proto-Oncogene Proteins