Although the silencing of either HIF-1α or HIF-2α negatively affected apoptosis resistance, tumor metabolism, migration, and the tumorigenic activity of several colon cancer cell lines, HIF-1α and HIF-2α deficiency also revealed isoform-specific effects on tumor cells, reinforcing the emerging concept that these two HIF isoforms can act antagonistically and not redundantly to regulate biological processes in malignancy [28]. This evidence concerns the gene EPAS1 and colonic neoplasm.