Oxygen sensing in cancer.
Hypoxia is prevalent in many tumours and is prognostically important. A transcriptional pathway controlled by hypoxia-inducible factor-1 (HIF) is also commonly up-regulated in cancer, resulting in the induction of genes with both pro- and anti-tumourigenic properties. High HIF levels may arise as a response to the tumour micro-environment or because of genetic events, including mutations affecting the von Hippel-Lindau tumour suppressor protein. Recent elucidation of mechanisms underlying the regulation of HIF, via amino acid hydroxylases, suggests a role in balancing energy production, iron metabolism and oxygen supply. Co-selection of properties linked by the HIF pathway may explain the glycolytic phenotype of tumours and underlie tumour angiogenesis, which though benefiting the tumour as a whole is unlikely to be directly selected at the clonal level because it will not give one cell specific advantage over its neighbours.
Henry Wellcome Building of Genomic Medicine, University of Oxford, Headington, UK. cpugh@well.ox.ac.uk
Christopher W
CW
Pugh
D000818:Animals; D015687:Cell Hypoxia; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009369:Neoplasms / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D006623:von Hippel-Lindau Disease / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D010100:Oxygen