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The Hippo Kinase LATS2 Controls Helicobacter pylori-Induced Epithelial-Mesenchymal Transition and Intestinal Metaplasia in Gastric Mucosa

hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorMOLINA-CASTRO, Silvia Elena
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorTIFFON, Camille
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorGIRAUD, Julie
hal.structure.identifierBioingénierie tissulaire [BIOTIS]
dc.contributor.authorBOEUF, Hélène
ORCID: 0000-0002-3006-8773
IDREF: 03205453X
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorSIFRE, Elodie
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorGIESE, Alban
hal.structure.identifierCentre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
dc.contributor.authorBELLEANNÉE, Geneviève
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorLEHOURS, Philippe
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorBESSÈDE, Emilie
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorMÉGRAUD, Francis
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorDUBUS, Pierre
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorSTAEDEL, Cathy
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorVARON, Christine
dc.date.accessioned2021-06-10T07:03:30Z
dc.date.available2021-06-10T07:03:30Z
dc.date.issued2020
dc.identifier.issn2352-345X
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/78919
dc.description.abstractEnBackground & aims: Gastric carcinoma is related mostly to CagA+-Helicobacter pylori infection, which disrupts the gastric mucosa turnover and elicits an epithelial-mesenchymal transition (EMT) and preneoplastic transdifferentiation. The tumor suppressor Hippo pathway controls stem cell homeostasis; its core, constituted by the large tumor suppressor 2 (LATS2) kinase and its substrate Yes-associated protein 1 (YAP1), was investigated in this context.Methods: Hippo, EMT, and intestinal metaplasia marker expression were investigated by transcriptomic and immunostaining analyses in human gastric AGS and MKN74 and nongastric immortalized RPE1 and HMLE epithelial cell lines challenged by H pylori, and on gastric tissues of infected patients and mice. LATS2 and YAP1 were silenced using small interfering RNAs. A transcriptional enhanced associated domain (TEAD) reporter assay was used. Cell proliferation and invasion were evaluated.Results: LATS2 and YAP1 appear co-overexpressed in the infected mucosa, especially in gastritis and intestinal metaplasia. H pylori via CagA stimulates LATS2 and YAP1 in a coordinated biphasic pattern, characterized by an early transient YAP1 nuclear accumulation and stimulated YAP1/TEAD transcription, followed by nuclear LATS2 up-regulation leading to YAP1 phosphorylation and targeting for degradation. LATS2 and YAP1 reciprocally positively regulate each other's expression. Loss-of-function experiments showed that LATS2 restricts H pylori-induced EMT marker expression, invasion, and intestinal metaplasia, supporting a role of LATS2 in maintaining the epithelial phenotype of gastric cells and constraining H pylori-induced preneoplastic changes.Conclusions: H pylori infection engages a number of signaling cascades that alienate mucosa homeostasis, including the Hippo LATS2/YAP1/TEAD pathway. In the host-pathogen conflict, which generates an inflammatory environment and perturbations of the epithelial turnover and differentiation, Hippo signaling appears as a protective pathway, limiting the loss of gastric epithelial cell identity that precedes gastric carcinoma development.
dc.language.isoen
dc.publisherPhiladelphia, PA : American Gastroenterological Association, [2015]-
dc.subject.enAdenocarcinoma
dc.subject.enCagA
dc.subject.enEpithelial-to-Mesenchymal Transition
dc.subject.enYAP1.
dc.title.enThe Hippo Kinase LATS2 Controls Helicobacter pylori-Induced Epithelial-Mesenchymal Transition and Intestinal Metaplasia in Gastric Mucosa
dc.typeArticle de revue
dc.identifier.doi10.1016/j.jcmgh.2019.10.007
dc.subject.halSciences du Vivant [q-bio]
bordeaux.journalCellular and Molecular Gastroenterology and Hepatology
bordeaux.page257-276
bordeaux.volume9
bordeaux.hal.laboratoriesBioingénierie Tissulaire (BioTis) - U1026*
bordeaux.issue2
bordeaux.institutionCNRS
bordeaux.institutionINSERM
bordeaux.institutionCHU de Bordeaux
bordeaux.institutionInstitut Bergonié
bordeaux.peerReviewedoui
hal.identifierinserm-03004849
hal.version1
hal.origin.linkhttps://hal.archives-ouvertes.fr//inserm-03004849v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Cellular%20and%20Molecular%20Gastroenterology%20and%20Hepatology&rft.date=2020&rft.volume=9&rft.issue=2&rft.spage=257-276&rft.epage=257-276&rft.eissn=2352-345X&rft.issn=2352-345X&rft.au=MOLINA-CASTRO,%20Silvia%20Elena&TIFFON,%20Camille&GIRAUD,%20Julie&BOEUF,%20H%C3%A9l%C3%A8ne&SIFRE,%20Elodie&rft.genre=article


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