Peroxisome Proliferator-Activated Receptor γ (PPARγ) mediates a Ski oncogene-induced shift from glycolysis to oxidative energy metabolism

Fang Ye, Hélène Lemieux, Charles L. Hoppel, Richard W. Hanson, Parvin Hakimi, Colleen M. Croniger, Michelle Puchowicz, Vernon E. Anderson, Hisashi Fujioka, Ed Stavnezer

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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 PPAR- 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.

Original languageEnglish (US)
Pages (from-to)40013-40024
Number of pages12
JournalJournal of Biological Chemistry
Volume286
Issue number46
DOIs
StatePublished - Nov 18 2011

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Peroxisome Proliferator-Activated Receptors
Glycolysis
Oncogenes
Energy Metabolism
Fibroblasts
Chickens
Embryonic Structures
Oxidation
Genes
Activity Cycles
Adipogenesis
Mitochondria
Organelle Biogenesis
Transcription
RNA Interference
Lipid Metabolism
Metabolism
Oxygen Consumption
Glutamic Acid
Lactic Acid

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Peroxisome Proliferator-Activated Receptor γ (PPARγ) mediates a Ski oncogene-induced shift from glycolysis to oxidative energy metabolism. / Ye, Fang; Lemieux, Hélène; Hoppel, Charles L.; Hanson, Richard W.; Hakimi, Parvin; Croniger, Colleen M.; Puchowicz, Michelle; Anderson, Vernon E.; Fujioka, Hisashi; Stavnezer, Ed.

In: Journal of Biological Chemistry, Vol. 286, No. 46, 18.11.2011, p. 40013-40024.

Research output: Contribution to journalArticle

Ye, F, Lemieux, H, Hoppel, CL, Hanson, RW, Hakimi, P, Croniger, CM, Puchowicz, M, Anderson, VE, Fujioka, H & Stavnezer, E 2011, 'Peroxisome Proliferator-Activated Receptor γ (PPARγ) mediates a Ski oncogene-induced shift from glycolysis to oxidative energy metabolism', Journal of Biological Chemistry, vol. 286, no. 46, pp. 40013-40024. https://doi.org/10.1074/jbc.M111.292029
Ye, Fang ; Lemieux, Hélène ; Hoppel, Charles L. ; Hanson, Richard W. ; Hakimi, Parvin ; Croniger, Colleen M. ; Puchowicz, Michelle ; Anderson, Vernon E. ; Fujioka, Hisashi ; Stavnezer, Ed. / Peroxisome Proliferator-Activated Receptor γ (PPARγ) mediates a Ski oncogene-induced shift from glycolysis to oxidative energy metabolism. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 46. pp. 40013-40024.
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