EPAS1 and cancer: Additionally, HAF has the ability to bind to and activate HIF-2α, driving the maximal expression of HIF-2α target genes (particularly of the HIF-2α dependent pluripotency genes OCT-3/4, SOX2,and NANOG), which can promote the enrichment of the cancer stem cell population, resulting in more aggressive tumors in vivo (Koh et al., 2015).