Hypoxia-regulated differentiation: let's step it up a Notch

Trends Mol Med. 2006 Apr;12(4):141-3. doi: 10.1016/j.molmed.2006.02.001. Epub 2006 Mar 2.


Although hypoxia is widely associated with adult pathologies such as cancer, it is also a physiological process that regulates cell differentiation during organogenesis. In an attempt to characterize the molecular mechanisms that are involved in hypoxia-regulated cell fate, a recent publication by Gustafsson and colleagues elegantly demonstrated that hypoxia blocks cell differentiation through the regulation of Notch signalling. This study showed that hypoxia-inducible factor (HIF)-1alpha interacts and acts in synergy with the Notch intracellular domain (NIC) and subsequently activates transcription of Notch targets. The identification of this crosstalk between pathways that are often deregulated in cancer is groundbreaking and opens up new areas for cancer research.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cell Hypoxia / physiology
  • Humans
  • Hypoxia-Inducible Factor 1 / genetics
  • Hypoxia-Inducible Factor 1 / metabolism
  • Hypoxia-Inducible Factor 1 / physiology*
  • Models, Biological
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism
  • Receptors, Notch / physiology*
  • Signal Transduction / physiology


  • Hypoxia-Inducible Factor 1
  • Receptors, Notch