Ye 2011 J Biol Chem
|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-induced shift from glycolysis to oxidative energy metabolism. J Biol Chem 286:40013-24.|
Abstract: Over-expression 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 to 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.
• Keywords: Chicken embryo fibroblasts (CEFs)
Labels: MiParea: Respiration, mt-Biogenesis;mt-density
Organism: Chicken Tissue;cell: Fibroblast Preparation: Intact cells
Regulation: Aerobic glycolysis Coupling state: ROUTINE