Notch tumor suppressor function

Oncogene. 2008 Sep 1;27(38):5115-23. doi: 10.1038/onc.2008.225.

Abstract

Cancer development results from deregulated control of stem cell populations and alterations in their surrounding environment. Notch signaling is an important form of direct cell-cell communication involved in cell fate determination, stem cell potential and lineage commitment. The biological function of this pathway is critically context dependent. Here we review the pro-differentiation role and tumor suppressing function of this pathway, as revealed by loss-of-function in keratinocytes and skin, downstream of p53 and in cross-connection with other determinants of stem cell potential and/or tumor formation, such as p63 and Rho/CDC42 effectors. The possibility that Notch signaling elicits a duality of signals, involved in growth/differentiation control and cell survival will be discussed, in the context of novel approaches for cancer therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cell Differentiation / physiology
  • Cell Transformation, Neoplastic / genetics
  • DNA Damage
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Keratinocytes / pathology
  • Keratinocytes / radiation effects
  • Mice
  • Neoplasms / genetics*
  • Neoplasms / physiopathology
  • Neoplasms / virology
  • Oncogene Proteins, Viral / physiology
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / physiology
  • Receptors, Notch / genetics
  • Receptors, Notch / physiology*
  • Signal Transduction / physiology
  • Species Specificity
  • Tumor Suppressor Protein p53 / physiology
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*
  • Tumor Virus Infections / physiopathology
  • Ultraviolet Rays / adverse effects
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / physiopathology
  • Uterine Cervical Neoplasms / virology

Substances

  • NOTCH1 protein, human
  • Notch1 protein, mouse
  • Oncogene Proteins, Viral
  • Receptor, Notch1
  • Receptors, Notch
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins