During VM formation in GBM, HIF2α and 1α regulate VE-cadherin expression by directly interacting with hypoxia responsive elements (HREs) in its promoter [31]; however, in aggressive melanoma, though hypoxia induces VM via VE-cadherin, VE-cadherin is up-regulated by Bcl-2 rather than HIFs [54]. This evidence concerns the gene CDH5 and melanoma.