| dc.rights.license | open | en_US |
| hal.structure.identifier | Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)] | |
| dc.contributor.author | SANCEAU, Julie | |
| hal.structure.identifier | Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)] | |
| dc.contributor.author | POUPEL, Lucie | |
| hal.structure.identifier | Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)] | |
| dc.contributor.author | JOUBEL, Camille | |
| hal.structure.identifier | Institut Cochin [IC UM3 (UMR 8104 / U1016)] | |
| dc.contributor.author | LAGOUTTE, Isabelle | |
| hal.structure.identifier | Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)] | |
| dc.contributor.author | CARUSO, Stefano | |
| hal.structure.identifier | Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)] | |
| dc.contributor.author | PINTO, Sandra | |
| hal.structure.identifier | Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)] | |
| dc.contributor.author | DESBOIS-MOUTHON, Christèle | |
| hal.structure.identifier | Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)] | |
| dc.contributor.author | GODARD, Cécile | |
| hal.structure.identifier | Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)] | |
| dc.contributor.author | HAMIMI, Akila | |
| hal.structure.identifier | Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)] | |
| dc.contributor.author | MONTMORY, Enzo | |
| hal.structure.identifier | Institut de Génomique d'Evry [IG] | |
| dc.contributor.author | DULARY, Cécile | |
| hal.structure.identifier | Institut de Génomique d'Evry [IG] | |
| dc.contributor.author | CHANTALAT, Sophie | |
| hal.structure.identifier | Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)] | |
| dc.contributor.author | ROEHRIG, Amélie | |
| hal.structure.identifier | Institut de Génomique d'Evry [IG] | |
| dc.contributor.author | MURET, Kevin | |
| hal.structure.identifier | Institut Cochin [IC UM3 (UMR 8104 / U1016)] | |
| dc.contributor.author | SAINT-PIERRE, Benjamin | |
| hal.structure.identifier | Institut de Génomique d'Evry [IG] | |
| dc.contributor.author | DELEUZE, Jean-François | |
| hal.structure.identifier | Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)] | |
| dc.contributor.author | MOUILLET-RICHARD, Sophie | |
| hal.structure.identifier | Institut de Génétique Moléculaire de Montpellier [IGMM] | |
| dc.contributor.author | FORNÉ, Thierry | |
| hal.structure.identifier | Biothérapies des maladies génétiques et cancers | |
| hal.structure.identifier | BoRdeaux Institute in onCology [Inserm U1312 - BRIC] | |
| dc.contributor.author | GROSSET, Christophe F. | |
| hal.structure.identifier | Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)] | |
| dc.contributor.author | COLNOT, Sabine | |
| hal.structure.identifier | Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)] | |
| dc.contributor.author | GOUGELET, Angélique | |
| dc.date.accessioned | 2025-06-13T08:33:28Z | |
| dc.date.available | 2025-06-13T08:33:28Z | |
| dc.date.issued | 2024-02-03 | |
| dc.identifier.issn | 1525-0016 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/206898 | |
| dc.description.abstractEn | The CTNNB1 gene, encoding β-catenin, is frequently mutated in hepatocellular carcinoma (HCC, ∼30%) and in hepatoblastoma (HB, >80%), in which DLK1/DIO3 locus induction is correlated with CTNNB1 mutations. Here, we aim to decipher how sustained β-catenin activation regulates DLK1/DIO3 locus expression and the role this locus plays in HB and HCC development in mouse models deleted for Apc (ApcΔhep) or Ctnnb1-exon 3 (β-cateninΔExon3) and in human CTNNB1-mutated hepatic cancer cells. We identified an enhancer site bound by TCF-4/β-catenin complexes in an open conformation upon sustained β-catenin activation (DLK1-WRE) and increasing DLK1/DIO3 locus transcription in β-catenin-mutated human HB and mouse models. DLK1-WRE editing by CRISPR/Cas9 approach impaired DLK1/DIO3 locus expression and slowed tumor growth in subcutaneous CTNNB1-mutated tumor cell grafts, ApcΔhep HB and β-cateninΔExon3 HCC. Tumor growth inhibition resulted either from increased FADD expression and subsequent caspase-3 cleavage in the first case, or from decreased expression of cell cycle actors regulated by FoxM1 in the others. Therefore, the DLK1/DIO3 locus is an essential determinant of FoxM1-dependent cell proliferation during β-catenin-driven liver tumorigenesis. Targeting the DLK1-WRE enhancer to silence the DLK1/DIO3 locus might thus represent an interesting therapeutic strategy to restrict tumor growth in primary liver cancers with CTNNB1 mutations. | |
| dc.language.iso | EN | en_US |
| dc.subject.en | primary liver cancers | |
| dc.subject.en | transgenic mice | |
| dc.subject.en | in vivo CRISPR/Cas9 | |
| dc.subject.en | β-catenin | |
| dc.subject.en | enhancer site | |
| dc.subject.en | non-coding RNAs | |
| dc.subject.en | targeted therapies | |
| dc.title.en | DLK1/DIO3 locus upregulation by a β-catenin-dependent enhancer drives cell proliferation and liver tumorigenesis | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1016/j.ymthe.2024.01.036 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio] | en_US |
| bordeaux.journal | Molecular Therapy | en_US |
| bordeaux.hal.laboratories | BRIC (Bordeaux of Institute of Oncology) - U1312 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | INSERM | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.import.source | hal | |
| hal.identifier | hal-04441676 | |
| hal.version | 1 | |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | false | |
| workflow.import.source | hal | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Molecular%20Therapy&rft.date=2024-02-03&rft.eissn=1525-0016&rft.issn=1525-0016&rft.au=SANCEAU,%20Julie&POUPEL,%20Lucie&JOUBEL,%20Camille&LAGOUTTE,%20Isabelle&CARUSO,%20Stefano&rft.genre=article | |
