As part of the physiological adaptive response, the PNN stimulates the stabilization of hypoxia-induced factors (HIFs), HIF1a and HIF2a, resulting in a driving force for activation of anti-apoptotic and pro-migratory transcriptional programs, supporting angiogenesis (35, 36), and re-expression of markers and properties typical of glioma stem cells (GSCs) (30, 37–42). This evidence concerns the gene HIF1A and central nervous system cancer.