Fig. 7

Schematic diagram illustrating insulin-induced PD-L1 up-regulation and EGF help in PD-L1 transport in colon CSCs. Insulin binds to its receptor IR and activates the IRS which phosphorylate the PI3K. Activated PI3K can activate AKT through PIP3 and phosphorylate AKT. A downstream target of AKT is mTOR, that can lead to activation and translocation of possible S6K into the nucleus [46, 47] and subsequent start of the PD-L1 transcription and PD-L1 protein production. Cytoplasmic PD-L1 proteins will be transferred to cell membrane through EGF/EGFR-mediated transport or stabilization on the cell membrane. Because BEZ235 can inhibit both AKT and mTOR thus reduce PD-L1 production via this pathway