However, both HIF-1α/2α were shown to be critical for CSC maintenance, as the knockdown of either HIF-1α or HIF-2α reduced self-renewal capacity, enhanced differentiation, attenuated tumorigenicity and increased apoptosis of glioma/glioblastoma and neuroblastoma TICs, resulting in less aggressive tumor phenotype [153, 154, 156, 158]. This evidence concerns the gene EPAS1 and neuroblastoma.