MTOR and central nervous system cancer: As metformin has also been reported to exert anti-glioma effects independently of AMPK, including a recent study demonstrating that metformin enhances binding of PRAS40 with RAPTOR protein resulting in mTOR inhibition and suppression of glioma cell proliferation, independently of AMPK [19], we wanted to determine the contribution of AMPK in our models using RNA interference strategy and previously validated siRNAs (Fig 5A) [22].