SCFFBW7α together with GSK3 regulate SOX9 protein levels through the ubiquitin-proteasome system. FBW7α mutations, such as those detected in SHH-medulloblastoma, lead to stabilization of SOX9 protein and subsequently promote SOX9-driven EMT-like reprogramming in medulloblastoma. Small molecule inhibitors of the PI3K/ mTOR pathway can be used to promote GSK3 / FBW7α-mediated SOX9 turnover and may provide a novel strategy to target SOX9-driven medulloblastoma. 