Loss of Fbxw7 synergizes with activated Akt signaling to promote c-Myc dependent cholangiocarcinogenesis

•Downregulation of the FBXW7 tumor suppressor gene was identified as a universal feature of human intrahepatic cholangiocarcinoma (iCCA). •Hydrodynamic transfection of inactivated Fbxw7 synergized with an activated form of AKT to induce rapid iCCA in mice. •Cholangiocarcinogenesis was prevented by c-Myc suppression, while being delayed by either Yap or Notch 2 depletion in these mice. •Inhibition of c-MYC might represent an innovative...