Epithelial mesenchymal transition and pancreatic tumor initiating CD44+/EpCAM+ cells are inhibited by γ-secretase inhibitor IX.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a high rate of metastasis. Recent studies have indicated that the Notch signalling pathway is important in PDAC initiation and maintenance, although the specific cell biological roles of the pathway remain to be established. Here...

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Autores principales:	Vindhya Palagani, Mona El Khatib, Uta Kossatz, Przemyslaw Bozko, Martin R Müller, Michael P Manns, Till Krech, Nisar P Malek, Ruben R Plentz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8ed258c7a23846cd9294727497d68a0f
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spelling	oai:doaj.org-article:8ed258c7a23846cd9294727497d68a0f2021-11-18T08:11:31ZEpithelial mesenchymal transition and pancreatic tumor initiating CD44+/EpCAM+ cells are inhibited by γ-secretase inhibitor IX.1932-620310.1371/journal.pone.0046514https://doaj.org/article/8ed258c7a23846cd9294727497d68a0f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23094026/?tool=EBIhttps://doaj.org/toc/1932-6203Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a high rate of metastasis. Recent studies have indicated that the Notch signalling pathway is important in PDAC initiation and maintenance, although the specific cell biological roles of the pathway remain to be established. Here we sought to examine this question in established pancreatic cancer cell lines using the γ-secretase inhibitor IX (GSI IX) to inactivate Notch. Based on the known roles of Notch in development and stem cell biology, we focused on effects on epithelial mesenchymal transition (EMT) and on pancreatic tumor initiating CD44+/EpCAM+ cells. We analyzed the effect of the GSI IX on growth and epithelial plasticity of human pancreatic cancer cell lines, and on the tumorigenicity of pancreatic tumor initiating CD44+/EpCAM+ cells. Notably, apoptosis was induced after GSI IX treatment and EMT markers were selectively targeted. Furthermore, under GSI IX treatment, decline in the growth of pancreatic tumor initiating CD44+/EpCAM+ cells was observed in vitro and in a xenograft mouse model. This study demonstrates a central role of Notch signalling pathway in pancreatic cancer pathogenesis and identifies an effective approach to inhibit selectively EMT and suppress tumorigenesis by eliminating pancreatic tumor initiating CD44+/EpCAM+ cells.Vindhya PalaganiMona El KhatibUta KossatzPrzemyslaw BozkoMartin R MüllerMichael P MannsTill KrechNisar P MalekRuben R PlentzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e46514 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vindhya Palagani Mona El Khatib Uta Kossatz Przemyslaw Bozko Martin R Müller Michael P Manns Till Krech Nisar P Malek Ruben R Plentz Epithelial mesenchymal transition and pancreatic tumor initiating CD44+/EpCAM+ cells are inhibited by γ-secretase inhibitor IX.
description	Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a high rate of metastasis. Recent studies have indicated that the Notch signalling pathway is important in PDAC initiation and maintenance, although the specific cell biological roles of the pathway remain to be established. Here we sought to examine this question in established pancreatic cancer cell lines using the γ-secretase inhibitor IX (GSI IX) to inactivate Notch. Based on the known roles of Notch in development and stem cell biology, we focused on effects on epithelial mesenchymal transition (EMT) and on pancreatic tumor initiating CD44+/EpCAM+ cells. We analyzed the effect of the GSI IX on growth and epithelial plasticity of human pancreatic cancer cell lines, and on the tumorigenicity of pancreatic tumor initiating CD44+/EpCAM+ cells. Notably, apoptosis was induced after GSI IX treatment and EMT markers were selectively targeted. Furthermore, under GSI IX treatment, decline in the growth of pancreatic tumor initiating CD44+/EpCAM+ cells was observed in vitro and in a xenograft mouse model. This study demonstrates a central role of Notch signalling pathway in pancreatic cancer pathogenesis and identifies an effective approach to inhibit selectively EMT and suppress tumorigenesis by eliminating pancreatic tumor initiating CD44+/EpCAM+ cells.
format	article
author	Vindhya Palagani Mona El Khatib Uta Kossatz Przemyslaw Bozko Martin R Müller Michael P Manns Till Krech Nisar P Malek Ruben R Plentz
author_facet	Vindhya Palagani Mona El Khatib Uta Kossatz Przemyslaw Bozko Martin R Müller Michael P Manns Till Krech Nisar P Malek Ruben R Plentz
author_sort	Vindhya Palagani
title	Epithelial mesenchymal transition and pancreatic tumor initiating CD44+/EpCAM+ cells are inhibited by γ-secretase inhibitor IX.
title_short	Epithelial mesenchymal transition and pancreatic tumor initiating CD44+/EpCAM+ cells are inhibited by γ-secretase inhibitor IX.
title_full	Epithelial mesenchymal transition and pancreatic tumor initiating CD44+/EpCAM+ cells are inhibited by γ-secretase inhibitor IX.
title_fullStr	Epithelial mesenchymal transition and pancreatic tumor initiating CD44+/EpCAM+ cells are inhibited by γ-secretase inhibitor IX.
title_full_unstemmed	Epithelial mesenchymal transition and pancreatic tumor initiating CD44+/EpCAM+ cells are inhibited by γ-secretase inhibitor IX.
title_sort	epithelial mesenchymal transition and pancreatic tumor initiating cd44+/epcam+ cells are inhibited by γ-secretase inhibitor ix.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/8ed258c7a23846cd9294727497d68a0f
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Epithelial mesenchymal transition and pancreatic tumor initiating CD44+/EpCAM+ cells are inhibited by γ-secretase inhibitor IX.

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