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TAZ Controls Helicobacter pylori-Induced Epithelial–Mesenchymal Transition and Cancer Stem Cell-Like Invasive and Tumorigenic Properties

Helicobacter pylori infection, the main risk factor for gastric cancer (GC), leads to an epithelial–mesenchymal transition (EMT) of gastric epithelium contributing to gastric cancer stem cell (CSC) emergence. The Hippo pathway effectors yes-associated protein (YAP) and transcriptional co-activator w...

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Autores principales: Tiffon, Camille, Giraud, Julie, Molina-Castro, Silvia Elena, Peru, Sara, Seeneevassen, Lornella, Sifré, Elodie, Staedel, Cathy, Bessède, Emilie, Dubus, Pierre, Mégraud, Francis, Lehours, Philippe, Martin, Océane C.B., Varon, Christine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348942/
https://www.ncbi.nlm.nih.gov/pubmed/32545795
http://dx.doi.org/10.3390/cells9061462
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author Tiffon, Camille
Giraud, Julie
Molina-Castro, Silvia Elena
Peru, Sara
Seeneevassen, Lornella
Sifré, Elodie
Staedel, Cathy
Bessède, Emilie
Dubus, Pierre
Mégraud, Francis
Lehours, Philippe
Martin, Océane C.B.
Varon, Christine
author_facet Tiffon, Camille
Giraud, Julie
Molina-Castro, Silvia Elena
Peru, Sara
Seeneevassen, Lornella
Sifré, Elodie
Staedel, Cathy
Bessède, Emilie
Dubus, Pierre
Mégraud, Francis
Lehours, Philippe
Martin, Océane C.B.
Varon, Christine
author_sort Tiffon, Camille
collection PubMed
description Helicobacter pylori infection, the main risk factor for gastric cancer (GC), leads to an epithelial–mesenchymal transition (EMT) of gastric epithelium contributing to gastric cancer stem cell (CSC) emergence. The Hippo pathway effectors yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ) control cancer initiation and progression in many cancers including GC. Here, we investigated the role of TAZ in the early steps of H. pylori-mediated gastric carcinogenesis. TAZ implication in EMT, invasion, and CSC-related tumorigenic properties were evaluated in three gastric epithelial cell lines infected by H. pylori. We showed that H. pylori infection increased TAZ nuclear expression and transcriptional enhancer TEA domain (TEAD) transcription factors transcriptional activity. Nuclear TAZ and zinc finger E-box-binding homeobox 1 (ZEB1) were co-overexpressed in cells harboring a mesenchymal phenotype in vitro, and in areas of regenerative hyperplasia in gastric mucosa of H. pylori-infected patients and experimentally infected mice, as well as at the invasive front of gastric carcinoma. TAZ silencing reduced ZEB1 expression and EMT phenotype, and strongly inhibited invasion and tumorsphere formation induced by H. pylori. In conclusion, TAZ activation in response to H. pylori infection contributes to H. pylori-induced EMT, invasion, and CSC-like tumorigenic properties. TAZ overexpression in H. pylori-induced pre-neoplastic lesions and in GC could therefore constitute a biomarker of early transformation in gastric carcinogenesis.
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spelling pubmed-73489422020-07-22 TAZ Controls Helicobacter pylori-Induced Epithelial–Mesenchymal Transition and Cancer Stem Cell-Like Invasive and Tumorigenic Properties Tiffon, Camille Giraud, Julie Molina-Castro, Silvia Elena Peru, Sara Seeneevassen, Lornella Sifré, Elodie Staedel, Cathy Bessède, Emilie Dubus, Pierre Mégraud, Francis Lehours, Philippe Martin, Océane C.B. Varon, Christine Cells Article Helicobacter pylori infection, the main risk factor for gastric cancer (GC), leads to an epithelial–mesenchymal transition (EMT) of gastric epithelium contributing to gastric cancer stem cell (CSC) emergence. The Hippo pathway effectors yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ) control cancer initiation and progression in many cancers including GC. Here, we investigated the role of TAZ in the early steps of H. pylori-mediated gastric carcinogenesis. TAZ implication in EMT, invasion, and CSC-related tumorigenic properties were evaluated in three gastric epithelial cell lines infected by H. pylori. We showed that H. pylori infection increased TAZ nuclear expression and transcriptional enhancer TEA domain (TEAD) transcription factors transcriptional activity. Nuclear TAZ and zinc finger E-box-binding homeobox 1 (ZEB1) were co-overexpressed in cells harboring a mesenchymal phenotype in vitro, and in areas of regenerative hyperplasia in gastric mucosa of H. pylori-infected patients and experimentally infected mice, as well as at the invasive front of gastric carcinoma. TAZ silencing reduced ZEB1 expression and EMT phenotype, and strongly inhibited invasion and tumorsphere formation induced by H. pylori. In conclusion, TAZ activation in response to H. pylori infection contributes to H. pylori-induced EMT, invasion, and CSC-like tumorigenic properties. TAZ overexpression in H. pylori-induced pre-neoplastic lesions and in GC could therefore constitute a biomarker of early transformation in gastric carcinogenesis. MDPI 2020-06-13 /pmc/articles/PMC7348942/ /pubmed/32545795 http://dx.doi.org/10.3390/cells9061462 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tiffon, Camille
Giraud, Julie
Molina-Castro, Silvia Elena
Peru, Sara
Seeneevassen, Lornella
Sifré, Elodie
Staedel, Cathy
Bessède, Emilie
Dubus, Pierre
Mégraud, Francis
Lehours, Philippe
Martin, Océane C.B.
Varon, Christine
TAZ Controls Helicobacter pylori-Induced Epithelial–Mesenchymal Transition and Cancer Stem Cell-Like Invasive and Tumorigenic Properties
title TAZ Controls Helicobacter pylori-Induced Epithelial–Mesenchymal Transition and Cancer Stem Cell-Like Invasive and Tumorigenic Properties
title_full TAZ Controls Helicobacter pylori-Induced Epithelial–Mesenchymal Transition and Cancer Stem Cell-Like Invasive and Tumorigenic Properties
title_fullStr TAZ Controls Helicobacter pylori-Induced Epithelial–Mesenchymal Transition and Cancer Stem Cell-Like Invasive and Tumorigenic Properties
title_full_unstemmed TAZ Controls Helicobacter pylori-Induced Epithelial–Mesenchymal Transition and Cancer Stem Cell-Like Invasive and Tumorigenic Properties
title_short TAZ Controls Helicobacter pylori-Induced Epithelial–Mesenchymal Transition and Cancer Stem Cell-Like Invasive and Tumorigenic Properties
title_sort taz controls helicobacter pylori-induced epithelial–mesenchymal transition and cancer stem cell-like invasive and tumorigenic properties
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348942/
https://www.ncbi.nlm.nih.gov/pubmed/32545795
http://dx.doi.org/10.3390/cells9061462
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