The role of Notch in tumorigenesis: oncogene or tumour suppressor?
- 1 December 2003
- journal article
- review article
- Published by Springer Science and Business Media LLC 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
This publication has 135 references indexed in Scilit:
- Jagged-1 mediated activation of notch signaling induces complete maturation of human keratinocytes through NF-κB and PPARγCell Death & Differentiation, 2002
- Repression of Activator Protein-1-mediated Transcriptional Activation by the Notch-1 Intracellular DomainPublished by Elsevier BV ,2002
- Biological activities and molecular targets of the human papillomavirus E7 oncoproteinOncogene, 2001
- Notchic-ER chimeras display hormone-dependent transformation, nuclear accumulation, phosphorylation and CBF1 activationOncogene, 2000
- Identification of a novel NOTCH-4/INT-3 RNA species encoding an activated gene product in certain human tumor cell linesOncogene, 2000
- Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4aCell, 1997
- Frequent provirus insertional mutagenesis of Notch1 in thymomas of MMTVD/myc transgenic mice suggests a collaboration of c-myc and Notch1 for oncogenesis.Genes & Development, 1996
- Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity.Genes & Development, 1995
- TAN-1, the human homolog of the Drosophila Notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasmsCell, 1991
- Nucleotide sequence from the neurogenic locus Notch implies a gene product that shares homology with proteins containing EGF-like repeatsCell, 1985