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Emerging role of oncogenic ß-catenin in exosome biogenesis as a driver of immune escape in hepatocellular carcinoma

dc.rights.licenseopenen_US
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorDANTZER, Camille
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorVACHÉ, Justine
hal.structure.identifierContrôle de l’Activation Cellulaire, Progression Tumorale et Résistance thérapeutique [CAPTuR]
dc.contributor.authorBRUNEL, Aude
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorMAHOUCHE, Isabelle
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorRAYMOND, Anne-Aurélie
hal.structure.identifierPlateforme Protéome [Bordeaux]
dc.contributor.authorDUPUY, Jean-William
hal.structure.identifierBordeaux Imaging Center [BIC]
dc.contributor.authorPETREL, Melina
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorBIOULAC-SAGE, Paulette
hal.structure.identifierInterdisciplinary Institute for Neuroscience / Institut interdisciplinaire de neurosciences [Bordeaux] [IINS]
dc.contributor.authorPERRAIS, David
hal.structure.identifierTBM-Core [Bordeaux] [UMS3427 - INSERM US005]
dc.contributor.authorDUGOT-SENANT, Nathalie
hal.structure.identifierContrôle de l’Activation Cellulaire, Progression Tumorale et Résistance thérapeutique [CAPTuR]
dc.contributor.authorVERDIER, Mireille
hal.structure.identifierContrôle de l’Activation Cellulaire, Progression Tumorale et Résistance thérapeutique [CAPTuR]
dc.contributor.authorBESSETTE, Barbara
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorBILLOTTET, Clotilde
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorMOREAU, Violaine
dc.date.accessioned2025-06-13T08:38:30Z
dc.date.available2025-06-13T08:38:30Z
dc.date.issued2024
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/206899
dc.description.abstractEnImmune checkpoint inhibitors have produced encouraging results in cancer patients. However, the majority of ß-catenin-mutated tumors have been described as lacking immune infiltrates and resistant to immunotherapy. The mechanisms by which oncogenic ß-catenin affects immune surveillance remain unclear. Herein, we highlighted the involvement of ß-catenin in the regulation of the exosomal pathway and, by extension, in immune/cancer cell communication in hepatocellular carcinoma (HCC). We showed that mutated ß-catenin represses expression of SDC4 and RAB27A , two main actors in exosome biogenesis, in both liver cancer cell lines and HCC patient samples. Using nanoparticle tracking analysis and live-cell imaging, we further demonstrated that activated ß-catenin represses exosome release. Then, we demonstrated in 3D spheroid models that activation of β-catenin promotes a decrease in immune cell infiltration through a defect in exosome secretion. Taken together, our results provide the first evidence that oncogenic ß-catenin plays a key role in exosome biogenesis. Our study gives new insight into the impact of ß-catenin mutations on tumor microenvironment remodeling, which could lead to the development of new strategies to enhance immunotherapeutic response.Author's response and modifications : https://doi.org/10.7554/elife.95191.3.sa4
dc.language.isoENen_US
dc.rights.urihttp://creativecommons.org/licenses/by/
dc.title.enEmerging role of oncogenic ß-catenin in exosome biogenesis as a driver of immune escape in hepatocellular carcinoma
dc.typeArticle de revueen_US
dc.identifier.doi10.7554/eLife.95191en_US
dc.subject.halSciences du Vivant [q-bio]/Canceren_US
dc.subject.halSciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Génomique, Transcriptomique et Protéomique [q-bio.GN]en_US
dc.subject.halSciences du Vivant [q-bio]/Immunologie/Immunité adaptativeen_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologie/Hépatologie et Gastroentérologieen_US
bordeaux.journaleLifeen_US
bordeaux.page95191en_US
bordeaux.volume13en_US
bordeaux.hal.laboratoriesBRIC (Bordeaux of Institute of Oncology) - U1312en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierhal-04801200
hal.version1
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=eLife&rft.date=2024&rft.volume=13&rft.spage=95191&rft.epage=95191&rft.au=DANTZER,%20Camille&VACH%C3%89,%20Justine&BRUNEL,%20Aude&MAHOUCHE,%20Isabelle&RAYMOND,%20Anne-Aur%C3%A9lie&rft.genre=article


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