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HIF1A

MIM.603348 14q21-q24

Sunday 8 May 2005

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

- Human cancers converge at the HIF-2alpha oncogenic axis. Franovic A, Holterman CE, Payette J, Lee S. Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21306-11. PMID: 19955413 [Free]

- 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