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Article

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

1
INSERM, UMR1053 Bordeaux Research in Translational Oncology, BaRITOn, University of Bordeaux, F33000 Bordeaux, France
2
Institute for Health Research, University of Costa Rica, Sabanilla 11502, Costa Rica
3
INSERM, UMR1212, University of Bordeaux, F-33000 Bordeaux, France
4
CHU de Bordeaux, F-33000 Bordeaux, France
*
Author to whom correspondence should be addressed.
Cells 2020, 9(6), 1462; https://doi.org/10.3390/cells9061462
Received: 1 May 2020 / Revised: 1 June 2020 / Accepted: 10 June 2020 / Published: 13 June 2020
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Cancers: Gastric Cancer)
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. View Full-Text
Keywords: gastric cancer; Helicobacter pylori; hippo pathway; ZEB1; epithelial–mesenchymal transition; TAZ; WWTR1; cancer stem cells; YAP gastric cancer; Helicobacter pylori; hippo pathway; ZEB1; epithelial–mesenchymal transition; TAZ; WWTR1; cancer stem cells; YAP
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MDPI and ACS Style

Tiffon, C.; Giraud, J.; Molina-Castro, S.E.; Peru, S.; Seeneevassen, L.; Sifré, E.; Staedel, C.; Bessède, E.; Dubus, P.; Mégraud, F.; Lehours, P.; Martin, O.C.B.; Varon, C. TAZ Controls Helicobacter pylori-Induced Epithelial–Mesenchymal Transition and Cancer Stem Cell-Like Invasive and Tumorigenic Properties. Cells 2020, 9, 1462. https://doi.org/10.3390/cells9061462

AMA Style

Tiffon C, Giraud J, Molina-Castro SE, Peru S, Seeneevassen L, Sifré E, Staedel C, Bessède E, Dubus P, Mégraud F, Lehours P, Martin OCB, Varon C. TAZ Controls Helicobacter pylori-Induced Epithelial–Mesenchymal Transition and Cancer Stem Cell-Like Invasive and Tumorigenic Properties. Cells. 2020; 9(6):1462. https://doi.org/10.3390/cells9061462

Chicago/Turabian Style

Tiffon, Camille, Julie Giraud, Silvia E. Molina-Castro, Sara Peru, Lornella Seeneevassen, Elodie Sifré, Cathy Staedel, Emilie Bessède, Pierre Dubus, Francis Mégraud, Philippe Lehours, Océane C.B. Martin, and Christine Varon. 2020. "TAZ Controls Helicobacter pylori-Induced Epithelial–Mesenchymal Transition and Cancer Stem Cell-Like Invasive and Tumorigenic Properties" Cells 9, no. 6: 1462. https://doi.org/10.3390/cells9061462

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