VHL and renal cell carcinoma: In RCC, the loss of pVHL thus mimics hypoxia and leads to excess HIF activity and the subsequent activation of the transcription of hundreds of HIF target genes that participate in angiogenesis, cell migration, epithelial–mesenchymal transition (EMT), extracellular matrix remodeling, glucose and lipid metabolism, immune evasion, and metastasis [12].