Hypoxia-inducible factor-1 and oncogenic signalling

Bioessays. 2004 Mar;26(3):262-9. doi: 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-1alpha, 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-1alpha. In recent years, it has become clear that an extensive network of signalling cascades converge on HIF-1alpha to regulate the transcriptional response. A better understanding of this regulation may provide a basis for the development of new cancer therapies.

Publication types

  • Review

MeSH terms

  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Enzyme Activation
  • Growth Substances / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Mitogen-Activated Protein Kinases / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction / physiology*
  • Transcription Factors*

Substances

  • DNA-Binding Proteins
  • Growth Substances
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Protein Subunits
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Phosphatidylinositol 3-Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases