In this context, we defined the intracellular signalling pathway that controls ETBR-induced PHD2 regulation in melanoma cells demonstrating that the inhibition of ILK/AKT/mTOR pathway antagonizes the ETs-induced HIF-1α stability and VEGF expression and restores PHD2 promoter activity and protein expression inhibited by ETs (Figure 7). This evidence concerns the gene AKT1 and melanoma.