Hypoxia-inducible factor 1 (HIF-1) controls oxygen delivery (via angiogenesis) and metabolic adaptation to hypoxia (via glycolysis).

HIF-1 consists of a constitutively expressed HIF-1 beta subunit and an oxygen- and growth-factor-regulated HIF-1 alpha subunit.

Pathology

 In xenografts, tumor growth and angiogenesis are correlated with HIF-1 expression. In human cancers, HIF-1 alpha is overexpressed as a result of intratumoral hypoxia and genetic alterations affecting key oncogenes and tumor suppressor genes.

 HIF-1 alpha overexpression in biopsies of brain, breast, cervical, esophageal, oropharyngeal and ovarian cancers is correlated with treatment failure and mortality.

 Increased HIF-1 activity promotes tumor progression.

References

 Poellinger L, Johnson RS. HIF-1 and hypoxic response: the plot thickens. Curr Opin Genet Dev. 2004 Feb;14(1):81-5. PMID: #15108809#

 Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003 Oct;3(10):721-32. PMID: #13130303#

 Semenza GL. HIF-1 and tumor progression: pathophysiology and therapeutics. Trends Mol Med. 2002;8(4 Suppl):S62-7. PMID: #11927290#

 Semenza GL. Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology. Trends Mol Med. 2001 Aug;7(8):345-50. PMID: #11516994#