HIF1A and neoplasm: PI3K upregulates HIF-1α protein synthesis via AKT/mTOR and the eukaryotic translation initiation factor 4E (eIF-4E) binding protein (4E-BP1) Nevertheless, the activation of AKT could also lead to increased HIF-1α expression in tumor cells via another pathway that is independent of mTOR activation [88,89,90,91,92,93].