Fig. 2

The hypoxic cancer stem cells (CSC) niches on CSC regulation. HIF-1α plays an important role in hypoxic process. Under normoxic conditions, HIF-1α is hydroxylated and inactivated by the function of poly1 hydroxylase domain-containing enzymes (PHDs) and Factor Inhibiting HIF (FIH1), and finally results in degradation. Under hypoxic conditions, both PHDs and FIH1 are inactivated, and HIF-1α stabilizes with the function of Reactive Oxygen Spices (ROS). HIF-1α could also be activated via activation of the PI-3 kinase/Akt-signaling pathway, which is induced by growth factor signaling. The stabilized HIF-1α translocates from cytoplasm to nucleus, where it dimerizes with HIF-1β and bind to Hypoxia Response Element (HRE). The heterodimer activates the downstream target genes transcription at these sites upon cofactor (CBP/p300) recruitment. These target genes in hypoxic niche, including Vascular Endothelial Growth Factor (VEGF), Glucose Transporter 1 (GLUT1), SOX2, Nanog and Octamer-binding Transcription Factor 4 (OCT4), may determine the fate of CSCs such as angiogenesis, self-renewal, tumorigenicity and induced therapy resistance