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.