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.
Pugh
Christopher W
CW
Henry Wellcome Building of Genomic Medicine, University of Oxford, Headington, UK. cpugh@well.ox.ac.uk
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