HIF1A and cancer: In normal tissue, VHL causes proteolysis of HIF-1α, but in RCC, VHL inactivation is associated with higher levels of HIF-1α, increased transcription of genes implicated in angiogenesis and tumorigenesis, such as VEGF and PDGF as well as activation of the PI3-K/PKB/mTOR pathway, that is involved in cancer progression (57).