HIF1A
MIM.603348 14q21-q24
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.
Hypoxia-inducible factor (HIF)-1alpha (HIF1A) interacts and acts in synergy with the Notch intracellular domain (NIC) and subsequently activates transcription of Notch targets.
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
Lee DW, Andersen JK. Role of HIF-1 in iron regulation: potential therapeutic strategy for neurodegenerative disorders. Curr Mol Med. 2006 Dec;6(8):883-93. PMID: #17168739#
Sainson RC, Harris AL. Hypoxia-regulated differentiation: let’s step it up a Notch. Trends Mol Med. 2006 Apr;12(4):141-3. PMID: #16513423#
Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med. 2003 Jun;9(6):677-84. PMID: #12778166#
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#