EPAS1 and cancer: HIF-1α and HIF-2α are induced by hypoxia and coordinate the expression of numerous downstream genes that promote cancer cell invasion and angiogenesis, thereby shifting the cancer cells towards a metastatic phenotype.90 Specifically for the regulation of EMT, HIF-1α is reported to upregulate EMT-related transcription factors, such as Slug, TWIST and Snail in lung cancer,90 encoding them as repressors that block the expression of E-cadherin, which promote a flexible cytoskeleton and the characteristics of a mesenchymal phenotype (Fig. 3).