Fig. 2

Potential molecular mechanism of autophagy induction in the presence of RTK inhibitors. One of the pathways through which autophagy could be induced after RTK inhibition is PI3K/AKT/mTOR, which, in addition to other roles, blocks the initiation of autophagy. The initial step of autophagy is regulated by the ULK kinase complex, which is comprised of ULK, ATG13, and FIP200. This step is followed by the alignment of additional proteins that form the Vps34 complex (Vps34, Beclin-1, and Atg14L), which is needed for phagophore creation. Afterwards, the phagophore progresses toward the autophagosome by recruiting other proteins (Atg12/Atg5/Atg16 and LC3) within the double-layered membrane. At this step, as the autophagosomal membrane is increasing in size, the cytosolic contents are engulfed, thereby filling up the autophagosome with degradable intracellular cargo. Completely matured autophagosomes then fuse to lysosomes, generating autolysosomes, which enables the degradation of the included cargo. In this way, diverse cellular molecules are recycled and made available for reuse by the cell. Additional bypass mechanisms that may lead to the induction of autophagy after the addition of RTK inhibitors are not excluded (interrupted arrow). Orange and yellow blocks represent RTK and inhibitors of autophagy, respectively