These findings are consistent with the hypotheses that HIF-1α participates in the induction of an EMT genetic program that allows cancer cells to acquire features of mesenchymal-like cells, and importantly, that HIF-1α and HIF-2α do not activate the same pathways to regulate stem cell maintenance or differentiation, arguing that these proteins play complementary and non-redundant roles in tumor biology. This evidence concerns the gene EPAS1 and cancer.