Acta Neuropathol (2012) 123:587–600 levels of PPARc, HKII, PKM2, and Glut4 were strongly reduced, consistent with Shh signaling being required for E2F1 activation and induction of glycolysis, and indicating that glycolysis is a property associated with CGNP proliferation. Thus far, our results indicate a requirement for E2F1 in the regulation of PPARc and the enzymes promoting glycolysis. As shown in Fig. 3, PPARc and glycolytic enzymes lie downstream of E2F1. We wished to determine whether the activity of PPARc is required for glycolytic marker up-regulation in CGNPs. It is known that treatment of cells with PPARc agonists such as rosiglitazone is associated with induction of glycolytic enzymes including Glut4 [8], although the precise mechanism through which this takes place is unknown. We carried out dose–response studies with the PPARc-speciﬁc inhibitor GW9662, which has been used in vitro and in vivo to inhibit PPARc and displays no activity towards other PPAR family members [23, 28]. As shown in Fig. 4b, treatment of CGNPs with 50 or 100 nM GW-9662 resulted in loss of detectable PPARc, 595 which was remarkably associated with reduced HKII, PKM2, and Glut4. Importantly, GW9662 treatment had no effect on HKI and also did not reduce levels of FASN, indicating that although both FASN and PPARc lie downstream of E2F1, PPARc and FASN are regulated independently. Notably, GW9662 treatment also reduced CGNP proliferation as indicated by diminished cyclin D2 levels. Thus, PPARc activity is required for glycolysis and ongoing cell division in CGNPs. Inhibition of PPARc impairs glycolysis in medulloblastoma and prolongs survival of tumor-bearing mice Our data in CGNPs show that PPARc is associated with a proliferative state, and that PPARc positively regulates glycolytic markers. Many tumor cells are known to exhibit high levels of glycolysis, and NeuroD2-SmoA1 medullo- blastomas are consistently highly proliferative. We wished to determine whether PPARc inhibition could impair Fig. 4 Glycolysis in CGNPs is Shh- and PPARc-dependent. a CGNP cultures were prepared for western blot analysis from PN 4/5 mice and incubated with vehicle (Veh), Shh (3 lg/ml) and/or Smoothened inhibitor cyclopamine (10 lg/ml). The lysates were blotted for the glycolytic and proliferative proteins. The presented work was repeated with several sets of CGNP lysates from PN 4/5 mice. b CGNP cultures were prepared for western blot analysis from PN 4/5 mice and incubated with vehicle (Veh), Shh (3 lg/ml) and/or PPARc antagonist GW9662 in increasing doses of 0, 50, and 100 nM 123