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Notch signaling is necessary for epithelial growth arrest by TGF-β
Transforming growth factor β (TGF-β) and Notch act as tumor suppressors by inhibiting epithelial cell proliferation. TGF-β additionally promotes tumor invasiveness and metastasis, whereas Notch supports oncogenic growth. We demonstrate that TGF-β and ectopic Notch1 receptor cooperatively arrest epit...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064026/ https://www.ncbi.nlm.nih.gov/pubmed/17325209 http://dx.doi.org/10.1083/jcb.200612129 |
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author | Niimi, Hideki Pardali, Katerina Vanlandewijck, Michael Heldin, Carl-Henrik Moustakas, Aristidis |
author_facet | Niimi, Hideki Pardali, Katerina Vanlandewijck, Michael Heldin, Carl-Henrik Moustakas, Aristidis |
author_sort | Niimi, Hideki |
collection | PubMed |
description | Transforming growth factor β (TGF-β) and Notch act as tumor suppressors by inhibiting epithelial cell proliferation. TGF-β additionally promotes tumor invasiveness and metastasis, whereas Notch supports oncogenic growth. We demonstrate that TGF-β and ectopic Notch1 receptor cooperatively arrest epithelial growth, whereas endogenous Notch signaling was found to be required for TGF-β to elicit cytostasis. Transcriptomic analysis after blocking endogenous Notch signaling uncovered several genes, including Notch pathway components and cell cycle and apoptosis factors, whose regulation by TGF-β requires an active Notch pathway. A prominent gene coregulated by the two pathways is the cell cycle inhibitor p21. Both transcriptional induction of the Notch ligand Jagged1 by TGF-β and endogenous levels of the Notch effector CSL contribute to p21 induction and epithelial cytostasis. Cooperative inhibition of cell proliferation by TGF-β and Notch is lost in human mammary cells in which the p21 gene has been knocked out. We establish an intimate involvement of Notch signaling in the epithelial cytostatic response to TGF-β. |
format | Text |
id | pubmed-2064026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20640262007-11-29 Notch signaling is necessary for epithelial growth arrest by TGF-β Niimi, Hideki Pardali, Katerina Vanlandewijck, Michael Heldin, Carl-Henrik Moustakas, Aristidis J Cell Biol Research Articles Transforming growth factor β (TGF-β) and Notch act as tumor suppressors by inhibiting epithelial cell proliferation. TGF-β additionally promotes tumor invasiveness and metastasis, whereas Notch supports oncogenic growth. We demonstrate that TGF-β and ectopic Notch1 receptor cooperatively arrest epithelial growth, whereas endogenous Notch signaling was found to be required for TGF-β to elicit cytostasis. Transcriptomic analysis after blocking endogenous Notch signaling uncovered several genes, including Notch pathway components and cell cycle and apoptosis factors, whose regulation by TGF-β requires an active Notch pathway. A prominent gene coregulated by the two pathways is the cell cycle inhibitor p21. Both transcriptional induction of the Notch ligand Jagged1 by TGF-β and endogenous levels of the Notch effector CSL contribute to p21 induction and epithelial cytostasis. Cooperative inhibition of cell proliferation by TGF-β and Notch is lost in human mammary cells in which the p21 gene has been knocked out. We establish an intimate involvement of Notch signaling in the epithelial cytostatic response to TGF-β. The Rockefeller University Press 2007-02-26 /pmc/articles/PMC2064026/ /pubmed/17325209 http://dx.doi.org/10.1083/jcb.200612129 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Niimi, Hideki Pardali, Katerina Vanlandewijck, Michael Heldin, Carl-Henrik Moustakas, Aristidis Notch signaling is necessary for epithelial growth arrest by TGF-β |
title | Notch signaling is necessary for epithelial growth arrest by TGF-β |
title_full | Notch signaling is necessary for epithelial growth arrest by TGF-β |
title_fullStr | Notch signaling is necessary for epithelial growth arrest by TGF-β |
title_full_unstemmed | Notch signaling is necessary for epithelial growth arrest by TGF-β |
title_short | Notch signaling is necessary for epithelial growth arrest by TGF-β |
title_sort | notch signaling is necessary for epithelial growth arrest by tgf-β |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064026/ https://www.ncbi.nlm.nih.gov/pubmed/17325209 http://dx.doi.org/10.1083/jcb.200612129 |
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