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Verteporfin targeting YAP1/TAZ‐TEAD transcriptional activity inhibits the tumorigenic properties of gastric cancer stem cells

hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorGIRAUD, Julie
hal.structure.identifierUniversidad de Costa Rica [UCR]
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorMOLINA‐CASTRO, Silvia
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorSEENEEVASSEN, Lornella
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorSIFRÉ, Elodie
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorIZOTTE, Julien
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorTIFFON, Camille
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorSTAEDEL, Cathy
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.authorFERNANDEZ, Solène
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorBARTHELEMY, Philippe
hal.structure.identifierCentre national français de référence pour les campylobacters et les hélicobactéries [Bordeaux]
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorMEGRAUD, Francis
hal.structure.identifierCentre national français de référence pour les campylobacters et les hélicobactéries [Bordeaux]
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorLEHOURS, Philippe
hal.structure.identifierCentre national français de référence pour les campylobacters et les hélicobactéries [Bordeaux]
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorDUBUS, Pierre
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorVARON, Christine
dc.date.accessioned2021-06-10T07:03:28Z
dc.date.available2021-06-10T07:03:28Z
dc.date.issued2019-11-06
dc.identifier.issn0020-7136
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/78918
dc.description.abstractEnGastric carcinomas (GC) are heterogeneous tumors, composed of a subpopulation of cluster of differentiation-44 (CD44)+ tumorigenic and chemoresistant cancer stem cells (CSC). YAP1 and TAZ oncoproteins (Y/T) interact with TEA domain family member 1 (TEAD) transcription factors to promote cell survival and proliferation in multiple tissues. Their activity and role in GC remain unclear. This work aimed to analyze Y/T-TEAD activity and molecular signature in gastric CSC, and to assess the effect of verteporfin, a Food and Drug Administration-approved drug preventing Y/T-TEAD interaction, on gastric CSC tumorigenic properties. Y/T-TEAD molecular signature was investigated using bioinformatical (KmPlot database), transcriptomic and immunostaining analyses in patient-derived GC and cell lines. Verteporfin effects on Y/T-TEAD transcriptional activity, CSC proliferation and tumorigenic properties were evaluated using in vitro tumorsphere assays and mouse models of patient-derived GC xenografts. High expressions of YAP1, TAZ, TEAD1, TEAD4 and their target genes were associated with low overall survival in nonmetastatic human GC patients (n = 444). This Y/T-TEAD molecular signature was enriched in CD44+ patient-derived GC cells and in cells resistant to conventional chemotherapy. Verteporfin treatment inhibited Y/T-TEAD transcriptional activity, cell proliferation and CD44 expression, and decreased the pool of tumorsphere-forming CD44+ /aldehyde dehydrogenase (ALDH)high gastric CSC. Finally, verteporfin treatment inhibited GC tumor growth in vivo; the residual tumor cells exhibited reduced expressions of CD44 and ALDH1, and more importantly, they were unable to initiate new tumorspheres in vitro. All these data demonstrate that Y/T-TEAD activity controls gastric CSC tumorigenic properties. The repositioning of verteporfin targeting YAP1/TAZ-TEAD activity could be a promising CSC-based strategy for the treatment of GC.
dc.language.isoen
dc.publisherWiley
dc.subject.enCD44
dc.subject.enCSC
dc.subject.engastric carcinoma
dc.subject.enhippo pathway
dc.subject.enpatient-derived xenografts
dc.title.enVerteporfin targeting YAP1/TAZ‐TEAD transcriptional activity inhibits the tumorigenic properties of gastric cancer stem cells
dc.typeArticle de revue
dc.identifier.doi10.1002/ijc.32667
dc.subject.halSciences du Vivant [q-bio]
bordeaux.journalInternational Journal of Cancer
bordeaux.page2255-2267
bordeaux.volume146
bordeaux.hal.laboratoriesBioingénierie Tissulaire (BioTis) - U1026*
bordeaux.issue8
bordeaux.institutionCNRS
bordeaux.institutionINSERM
bordeaux.institutionCHU de Bordeaux
bordeaux.institutionInstitut Bergonié
bordeaux.peerReviewedoui
hal.identifierinserm-03004854
hal.version1
hal.origin.linkhttps://hal.archives-ouvertes.fr//inserm-03004854v1
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