Peroxisome proliferator-activated receptor ? (PPAR?) 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 ?-oxidation, glutamate oxidation, oxygen consumption, as well as increased numbers and mass of mitochondria. Interestingly, expression of PPAR?, a key transcription factor that regulates adipogenesis and lipid metabolism, was dramatically elevated at both the mRNA and protein levels in Ski-CEFs. Accordingly, PPAR? target genes that are involved in lipid uptake, transport, and oxidation were also markedly up-regulated by Ski. Knocking down PPAR? 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 PPAR? and co-activates PPAR?-driven transcription.

SUBMITTER: Ye F 

PROVIDER: S-EPMC3220574 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature