Hypoxia‐inducible factor‐1 and oncogenic signalling
- 21 February 2004
- Vol. 26 (3) , 262-269
- https://doi.org/10.1002/bies.20002
Abstract
An understanding of underlying mechanisms involved in the activation of HIF‐1 in response to both hypoxic stress and oncogenic signals has important implications for how these processes may become deregulated in human cancer. Changes in microenvironmental stimuli such as hypoxia and growth factors in combination with genetic lesions, such as loss or inactivation of p53, PTEN or pVHL or oncogenic activation, can all lead to increased HIF‐1 activity. This provides cancer cells with a distinct advantage for survival and proliferation, resulting in their ability to form vascular tumours, which are aggressive and metastatic. Accordingly, upregulation of HIF‐1α, a key component of HIF‐1, correlates with a poor treatment outcome using conventional therapies. A variety of mechanisms exist that regulate expression of HIF‐1α. In recent years, it has become clear that an extensive network of signalling cascades converge on HIF‐1α to regulate the transcriptional response. A better understanding of this regulation may provide a basis for the development of new cancer therapies. BioEssays 26:262–269, 2004.Keywords
This publication has 69 references indexed in Scilit:
- Targeting HIF-1 for cancer therapyNature Reviews Cancer, 2003
- Tumor Necrosis Factor-α Causes Accumulation of a Ubiquitinated Form of Hypoxia Inducible Factor-1α through a Nuclear Factor-κB-Dependent PathwayMolecular Biology of the Cell, 2003
- MAPK Signaling Up-regulates the Activity of Hypoxia-inducible Factors by Its Effects on p300Journal of Biological Chemistry, 2003
- Normoxic induction of the hypoxia‐inducible factor 1α by insulin and interleukin‐1β involves the phosphatidylinositol 3‐kinase pathwayFEBS Letters, 2002
- Hypoxia — a key regulatory factor in tumour growthNature Reviews Cancer, 2002
- Regulation of Mammalian O2Homeostasis by Hypoxia-Inducible Factor 1Annual Review of Cell and Developmental Biology, 1999
- The basic-helix–loop–helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factorsProceedings of the National Academy of Sciences, 1998
- Transactivation and Inhibitory Domains of Hypoxia-inducible Factor 1αJournal of Biological Chemistry, 1997
- Activation of Hypoxia-inducible Transcription Factor Depends Primarily upon Redox-sensitive Stabilization of Its α SubunitJournal of Biological Chemistry, 1996
- Effect of Protein Kinase and Phosphatase Inhibitors on Expression of Hypoxia Inducible Factor 1Biochemical and Biophysical Research Communications, 1995