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Cytochrome P450 1B1 polymorphism drives cancer cell stemness and patient outcome in head-and-neck carcinoma

dc.rights.licenseopenen_US
hal.structure.identifierActions for OnCogenesis understanding and Target Identification in ONcology [ACTION]
dc.contributor.authorLE MORVAN, Valerie
hal.structure.identifierActions for OnCogenesis understanding and Target Identification in ONcology [ACTION]
dc.contributor.authorRICHARD, Elodie
hal.structure.identifierActions for OnCogenesis understanding and Target Identification in ONcology [ACTION]
dc.contributor.authorCADARS, Maud
hal.structure.identifierActions for OnCogenesis understanding and Target Identification in ONcology [ACTION]
dc.contributor.authorFESSART, Delphine
hal.structure.identifierActions for OnCogenesis understanding and Target Identification in ONcology [ACTION]
dc.contributor.authorBROCA-BRISSON, Lea
hal.structure.identifierActions for OnCogenesis understanding and Target Identification in ONcology [ACTION]
dc.contributor.authorAUZANNEAU, Celine
hal.structure.identifierActions for OnCogenesis understanding and Target Identification in ONcology [ACTION]
dc.contributor.authorPASQUIES, Alban
dc.contributor.authorMODESTO, A.
dc.contributor.authorLUSQUE, A.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorMATHOULIN-PELISSIER, Simone
hal.structure.identifierActions for OnCogenesis understanding and Target Identification in ONcology [ACTION]
dc.contributor.authorLANSIAUX, Amelie
hal.structure.identifierActions for OnCogenesis understanding and Target Identification in ONcology [ACTION]
dc.contributor.authorROBERT, Jacques
dc.date.accessioned2021-03-18T08:51:06Z
dc.date.available2021-03-18T08:51:06Z
dc.date.issued2020-09
dc.identifier.issn0007-0920en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/26719
dc.description.abstractEnBACKGROUND: Cytochrome P450 1B1 (CYP1B1) is mostly expressed in tumours and displays unusual properties. Its two polymorphic forms were differently associated with anticancer drug sensitivity. We decipher here the role of this polymorphism in anticancer drug efficacy in vitro, in vivo and in the clinical setting. METHODS: From head-and-neck squamous cell carcinoma cell lines not expressing CYP1B1, we generated isogenic derivatives expressing the two forms. Proliferation, invasiveness, stem cell characteristics, sensitivity to anticancer agents and transcriptome were analysed. Tumour growth and chemosensitivity were studied in vivo. A prospective clinical trial on 121 patients with advanced head-and-neck cancers was conducted, and a validation-retrospective study was conducted. RESULTS: Cell lines expressing the variant form displayed high rates of in vitro proliferation and invasiveness, stemness features and resistance to DNA-damaging agents. In vivo, tumours expressing the variant CYP1B1 had higher growth rates and were markedly drug-resistant. In the clinical study, overall survival was significantly associated with the genotypes, wild-type patients presenting a longer median survival (13.5 months) than the variant patients (6.3 months) (p = 0.0166). CONCLUSIONS: This frequent CYP1B1 polymorphism is crucial for cancer cell proliferation, migration, resistance to chemotherapy and stemness properties, and strongly influences head-and-neck cancer patients' survival.
dc.language.isoENen_US
dc.title.enCytochrome P450 1B1 polymorphism drives cancer cell stemness and patient outcome in head-and-neck carcinoma
dc.title.alternativeBr J Canceren_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41416-020-0932-5en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed32565541en_US
bordeaux.journalBritish Journal of Canceren_US
bordeaux.page772-784en_US
bordeaux.volume123en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.issue5en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamEPICENE_BPH
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03172919
hal.version1
hal.date.transferred2021-03-18T08:51:10Z
hal.exporttrue
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