Complete inhibition of mTORC1 cascade is required to suppress hepatocarcinogenesis induced by AKT and Ras co-expression

Introduction: AKT and Ras pathways are frequently concurrently hyperactivated in HCC. Previously, we have shown that co-expression of constitutively active forms of AKT (Myr-AKT) and activated Ras (N-RasV12) rapidly induces liver tumors in mice. mTORC1 is the main downstream effector of AKT, acting by phosphorylation of RPS-6 and 4E-BP1, and thus regulating cell metabolism, protein translation and other cellular processes. However, in which manner mTORC1 and its key downstream effectors RPS-6 and 4E-BP1/eIF4E do contribute to hepatocarcinogenesis remains unknown. Methods: Plasmids encoding Myr-AKT, RasV12, 4EBP1…