Activation of Notch signaling is required for cholangiocarcinoma progression and is enhanced by inactivation of p53 in vivo.

<h4>Unlabelled</h4>Cholangiocacinoma (CC) is a cancer disease with rising incidence. Notch signaling has been shown to be deregulated in many cancers. However, the role of this signaling pathway in the carcinogenesis of CC is still not fully explored. In this study, we investigated the e...

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Autores principales:	Mona El Khatib, Przemyslaw Bozko, Vindhya Palagani, Nisar P Malek, Ludwig Wilkens, Ruben R Plentz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/af72240344ee4beda97e4828529303f7
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spelling	oai:doaj.org-article:af72240344ee4beda97e4828529303f72021-11-18T08:49:01ZActivation of Notch signaling is required for cholangiocarcinoma progression and is enhanced by inactivation of p53 in vivo.1932-620310.1371/journal.pone.0077433https://doaj.org/article/af72240344ee4beda97e4828529303f72013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24204826/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Unlabelled</h4>Cholangiocacinoma (CC) is a cancer disease with rising incidence. Notch signaling has been shown to be deregulated in many cancers. However, the role of this signaling pathway in the carcinogenesis of CC is still not fully explored. In this study, we investigated the effects of Notch inhibition by γ-secretase inhibitor IX (GSI IX) in cultured human CC cell lines and we established a transgenic mouse model with liver specific expression of the intracellular domain of Notch (Notch-ICD) and inactivation of tumor suppressor p53. GSI IX treatment effectively impaired cell proliferation, migration, invasion, epithelial to mesenchymal transition and growth of softagar colonies. In vivo overexpression of Notch-ICD together with an inactivation of p53 significantly increased tumor burden and showed CC characteristics.<h4>Conclusion</h4>Our study highlights the importance of Notch signaling in the tumorigenesis of CC and demonstrates that additional inactivation of p53 in vivo.Mona El KhatibPrzemyslaw BozkoVindhya PalaganiNisar P MalekLudwig WilkensRuben R PlentzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 10, p e77433 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mona El Khatib Przemyslaw Bozko Vindhya Palagani Nisar P Malek Ludwig Wilkens Ruben R Plentz Activation of Notch signaling is required for cholangiocarcinoma progression and is enhanced by inactivation of p53 in vivo.
description	<h4>Unlabelled</h4>Cholangiocacinoma (CC) is a cancer disease with rising incidence. Notch signaling has been shown to be deregulated in many cancers. However, the role of this signaling pathway in the carcinogenesis of CC is still not fully explored. In this study, we investigated the effects of Notch inhibition by γ-secretase inhibitor IX (GSI IX) in cultured human CC cell lines and we established a transgenic mouse model with liver specific expression of the intracellular domain of Notch (Notch-ICD) and inactivation of tumor suppressor p53. GSI IX treatment effectively impaired cell proliferation, migration, invasion, epithelial to mesenchymal transition and growth of softagar colonies. In vivo overexpression of Notch-ICD together with an inactivation of p53 significantly increased tumor burden and showed CC characteristics.<h4>Conclusion</h4>Our study highlights the importance of Notch signaling in the tumorigenesis of CC and demonstrates that additional inactivation of p53 in vivo.
format	article
author	Mona El Khatib Przemyslaw Bozko Vindhya Palagani Nisar P Malek Ludwig Wilkens Ruben R Plentz
author_facet	Mona El Khatib Przemyslaw Bozko Vindhya Palagani Nisar P Malek Ludwig Wilkens Ruben R Plentz
author_sort	Mona El Khatib
title	Activation of Notch signaling is required for cholangiocarcinoma progression and is enhanced by inactivation of p53 in vivo.
title_short	Activation of Notch signaling is required for cholangiocarcinoma progression and is enhanced by inactivation of p53 in vivo.
title_full	Activation of Notch signaling is required for cholangiocarcinoma progression and is enhanced by inactivation of p53 in vivo.
title_fullStr	Activation of Notch signaling is required for cholangiocarcinoma progression and is enhanced by inactivation of p53 in vivo.
title_full_unstemmed	Activation of Notch signaling is required for cholangiocarcinoma progression and is enhanced by inactivation of p53 in vivo.
title_sort	activation of notch signaling is required for cholangiocarcinoma progression and is enhanced by inactivation of p53 in vivo.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/af72240344ee4beda97e4828529303f7
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Activation of Notch signaling is required for cholangiocarcinoma progression and is enhanced by inactivation of p53 in vivo.

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