Table 2.

HIF molecule expression patterns and the pathways they target.

HIF molecule	Expression pattern	Target genes	Pathways regulated	Refs
HIF-1 (induced under severe hypoxia 0-2% O2)- acute hypoxia response	Endothelial cells, tumour cells, immune cells (neutrophils/macrophages), fibroblasts and cancer stem cells	VEGF, CA9, BNIP3, GLUT-1, VEGF, uPAR, IGF1, PDGF-B, NDUFA4L2, HGF, ITGA6, P4HA1, P4HA2, PLOD2, LOX, syndecan-4, α5-integrin MMP-2, MMP9, MMP15, NFκB	Angiogenesis, acid metabolism, cell death, glycolysis, angiogenesis, proteolytic pathway of invasion, cell-ECM interactions, enhanced invasion and migration, fibrosis-enhanced metastasis, promote survival and function of neutrophils, enhanced cell survival	(23–36)
HIF-2 (induced over severe conditions 2-5%)- long term hypoxia response	Endothelial cells, tumour cells , fibroblasts, immune cells (neutrophils, macrophages), cancer stem cells	VEGF (more potent response than HIF-1), GLUT-1, UPAR1, ITGA6 , MMP14	Associated with long-term hypoxic response, angiogenesis, glycolysis, proteolytic pathway of invasion, cell-ECM interactions, vessel integrity and tumour neovascularisation, promote survival and function of neutrophils, regulator of innate immunity, and metastasis	(25, 26, 28, 29, 37–41)
HIF-3	Endothelial cells, tumour cells		Apoptosis, tumorigenesis, negative regulator of HIF-1/HIF-2 in renal cell carcinoma	(42–45)