When tumor is in hypoxic conditions, HIF-1α (HIF has two parts, a constitutive β-subunit and an oxygen-sensitive α subunit [15]) can not be hydroxylated by prolyl hydroxylase domain proteins and bounded by pVHL [89] because of Von Hippel-Lindau (VHL) gene mutation, then HIF-1α can not be in subsequent degradation by 26S proteasome [90–93]. Here, VHL is linked to neoplasm.