Verteporfin targeting YAP1/TAZ‐TEAD transcriptional activity inhibits the tumorigenic properties of gastric cancer stem cells
hal.structure.identifier | Bordeaux Research In Translational Oncology [Bordeaux] [BaRITOn] | |
dc.contributor.author | GIRAUD, Julie | |
hal.structure.identifier | Universidad de Costa Rica [UCR] | |
hal.structure.identifier | Bordeaux Research In Translational Oncology [Bordeaux] [BaRITOn] | |
dc.contributor.author | MOLINA‐CASTRO, Silvia | |
hal.structure.identifier | Bordeaux Research In Translational Oncology [Bordeaux] [BaRITOn] | |
dc.contributor.author | SEENEEVASSEN, Lornella | |
hal.structure.identifier | Bordeaux Research In Translational Oncology [Bordeaux] [BaRITOn] | |
dc.contributor.author | SIFRÉ, Elodie | |
hal.structure.identifier | Bordeaux Research In Translational Oncology [Bordeaux] [BaRITOn] | |
dc.contributor.author | IZOTTE, Julien | |
hal.structure.identifier | Bordeaux Research In Translational Oncology [Bordeaux] [BaRITOn] | |
dc.contributor.author | TIFFON, Camille | |
hal.structure.identifier | Acides Nucléiques : Régulations Naturelle et Artificielle [ARNA] | |
dc.contributor.author | STAEDEL, Cathy | |
hal.structure.identifier | Bioingénierie tissulaire [BIOTIS] | |
dc.contributor.author | BOEUF, Hélène
ORCID: 0000-0002-3006-8773 IDREF: 03205453X | |
hal.structure.identifier | Bordeaux Research In Translational Oncology [Bordeaux] [BaRITOn] | |
dc.contributor.author | FERNANDEZ, Solène | |
hal.structure.identifier | Acides Nucléiques : Régulations Naturelle et Artificielle [ARNA] | |
dc.contributor.author | BARTHELEMY, Philippe | |
hal.structure.identifier | Centre national français de référence pour les campylobacters et les hélicobactéries [Bordeaux] | |
hal.structure.identifier | Bordeaux Research In Translational Oncology [Bordeaux] [BaRITOn] | |
dc.contributor.author | MEGRAUD, Francis | |
hal.structure.identifier | Centre national français de référence pour les campylobacters et les hélicobactéries [Bordeaux] | |
hal.structure.identifier | Bordeaux Research In Translational Oncology [Bordeaux] [BaRITOn] | |
dc.contributor.author | LEHOURS, Philippe | |
hal.structure.identifier | Centre national français de référence pour les campylobacters et les hélicobactéries [Bordeaux] | |
hal.structure.identifier | Bordeaux Research In Translational Oncology [Bordeaux] [BaRITOn] | |
dc.contributor.author | DUBUS, Pierre | |
hal.structure.identifier | Bordeaux Research In Translational Oncology [Bordeaux] [BaRITOn] | |
dc.contributor.author | VARON, Christine | |
dc.date.accessioned | 2021-06-10T07:03:28Z | |
dc.date.available | 2021-06-10T07:03:28Z | |
dc.date.issued | 2019-11-06 | |
dc.identifier.issn | 0020-7136 | |
dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/78918 | |
dc.description.abstractEn | Gastric 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.iso | en | |
dc.publisher | Wiley | |
dc.subject.en | CD44 | |
dc.subject.en | CSC | |
dc.subject.en | gastric carcinoma | |
dc.subject.en | hippo pathway | |
dc.subject.en | patient-derived xenografts | |
dc.title.en | Verteporfin targeting YAP1/TAZ‐TEAD transcriptional activity inhibits the tumorigenic properties of gastric cancer stem cells | |
dc.type | Article de revue | |
dc.identifier.doi | 10.1002/ijc.32667 | |
dc.subject.hal | Sciences du Vivant [q-bio] | |
bordeaux.journal | International Journal of Cancer | |
bordeaux.page | 2255-2267 | |
bordeaux.volume | 146 | |
bordeaux.hal.laboratories | Bioingénierie Tissulaire (BioTis) - U1026 | * |
bordeaux.issue | 8 | |
bordeaux.institution | CNRS | |
bordeaux.institution | INSERM | |
bordeaux.institution | CHU de Bordeaux | |
bordeaux.institution | Institut Bergonié | |
bordeaux.peerReviewed | oui | |
hal.identifier | inserm-03004854 | |
hal.version | 1 | |
hal.origin.link | https://hal.archives-ouvertes.fr//inserm-03004854v1 | |
bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=International%20Journal%20of%20Cancer&rft.date=2019-11-06&rft.volume=146&rft.issue=8&rft.spage=2255-2267&rft.epage=2255-2267&rft.eissn=0020-7136&rft.issn=0020-7136&rft.au=GIRAUD,%20Julie&MOLINA%E2%80%90CASTRO,%20Silvia&SEENEEVASSEN,%20Lornella&SIFR%C3%89,%20Elodie&IZOTTE,%20Julien&rft.genre=article |
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