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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...

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Autores principales: Niimi, Hideki, Pardali, Katerina, Vanlandewijck, Michael, Heldin, Carl-Henrik, Moustakas, Aristidis
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
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.
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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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