EPAS1 and neoplasm: Hypoxia activates the transcription of HIF-1α and HIF-2α, which in turn induces CSC expansion by promoting the transcription of secreted proteins, citokines, non-coding RNAs and chemokines that will promote the adaptation of niches in different organs to receive, promote survival and adapt to proliferate malignant cells from the primary tumor, especially CSCs capable of regenerating the bulk of the tumor mass in the new emplacement, forming metastasis (Figure 3).