Figure 7. The putative model for the regulation of AKT/mTOR/c-Myc axis by PTEN and LKB1 in pNET.

PTEN and LKB1 can inhibit mTOR and its downstream effector, 4EBP1 and subsequent activation of c-Myc via inhibiting AKT activation and activating AMPK, respectively. However, c-Myc can activate mTOR through negatively back-regulating PTEN with activation of AKT or feedback activation of 4EBP1 directly and results in activation of c-Myc further. Metformin, an AMPK activator, can inhibit mTOR, 4EBP1 and c-Myc via activation of AMPK. 10058-F4, a c-Myc inhibitor, can also inhibit c-Myc and mTOR and 4EBP1 via inhibiting feedback regulation of mTOR and 4EBP1 by c-Myc.