The role of Notch in tumorigenesis: oncogene or tumour suppressor?
Top Cited Papers
- 1 December 2003
- journal article
- review article
- Published by Springer Nature in Nature Reviews Cancer
- Vol. 3 (10) , 756-767
- https://doi.org/10.1038/nrc1186
Abstract
Signalling between Notch receptors and ligands influences many differentiation processes and cell-fate decisions during embryonic and postnatal development. Stem-cell maintenance, binary cell-fate decisions and induction of differentiation are three main functions of Notch signalling in self-renewing tissues. Notch can function as an oncogene. Aberrant expression of the dominant active cytoplasmic domain of Notch receptors in haematopoietic cells because of chromosomal translocation or viral integrations causes T-cell leukaemias in mice and humans. Notch needs to cooperate with oncoproteins that can override the G1–S checkpoint in order to cause cancer. Notch receptors and ligands are re-expressed in certain human carcinomas, which is compatible with the ability of Notch to maintain stem cells or precursor cells in an undifferentiated state. Recent data show that Notch1 can also function as a tumour suppressor in mouse skin by inducing Waf1 and repressing Shh and Wnt signalling. Notch has two faces; one that promotes and the other that suppresses tumorigenesis. Which of the two faces is shown is dependent on the cellular context and the crosstalk with other signal-transduction pathways.Keywords
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