Fig. 1

The role of hypoxia in tumor angiogenesis. a Under normoxic conditions, HIF-1α and HIF-2α are hydroxylated by PHDs and FIH-1. Subsequently, pVHL can recognize and ubiquitinate hydroxylated HIF-1α/HIF-2α and degrade them via proteasome-mediated degradation. b Under hypoxic conditions, the inactivation of FIH-1 and PHDs cannot hydroxylate HIF-1/HIF-2α, decreases HIFα-VHL binding, and promotes the formation of HIFα-HIFβ dimers that enter the nucleus to activate downstream targets. HIF-1α/HIF-2α can activate EphA1, ANGPT, VEGFA, VEGFR1, and other angiogenesis related genes to promote tumor angiogenesis. Alternatively, HIF-1α/HIF-2α can activate Claudin-4, Vimentin, LOXL2, Twist1, VE-cadherin to promote vasculogenic mimicry