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dc.contributor.authorLazarus, Kyren A
dc.contributor.authorHadi, Fazal
dc.contributor.authorZambon, Elisabetta
dc.contributor.authorBach, Karsten
dc.contributor.authorSantolla, Maria-Francesca
dc.contributor.authorWatson, Julie
dc.contributor.authorCorreia, Lucia L
dc.contributor.authorDas, Madhumita
dc.contributor.authorUgur, Rosemary
dc.contributor.authorPensa, Sara
dc.contributor.authorBecker, Lukas
dc.contributor.authorCampos, Lia S
dc.contributor.authorLadds, Graham
dc.contributor.authorLiu, Pentao
dc.contributor.authorEvan, Gerard
dc.contributor.authorMcCaughan, Frank
dc.contributor.authorLe Quesne, John
dc.contributor.authorLee, Joo
dc.contributor.authorCalado, Dinis
dc.contributor.authorKhaled, Walid
dc.date.accessioned2018-09-20T12:05:11Z
dc.date.available2018-09-20T12:05:11Z
dc.date.issued2018-08-20
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/280493
dc.description.abstractPatients diagnosed with lung squamous cell carcinoma (LUSC) have limited targeted therapies. We report here the identification and characterisation of BCL11A, as a LUSC oncogene. Analysis of cancer genomics datasets revealed BCL11A to be upregulated in LUSC but not in lung adenocarcinoma (LUAD). Experimentally we demonstrate that non-physiological levels of BCL11A in vitro and in vivo promote squamous-like phenotypes, while its knockdown abolishes xenograft tumour formation. At the molecular level we found that BCL11A is transcriptionally regulated by SOX2 and is required for its oncogenic functions. Furthermore, we show that BCL11A and SOX2 regulate the expression of several transcription factors, including SETD8. We demonstrate that shRNA-mediated or pharmacological inhibition of SETD8 selectively inhibits LUSC growth. Collectively, our study indicates that BCL11A is integral to LUSC pathology and highlights the disruption of the BCL11A-SOX2 transcriptional programme as a novel candidate for drug development.
dc.description.sponsorshipCancer Research UK (CRUK) - C47525/A17348
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.subjectLung
dc.subjectOrganoids
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectCarcinoma, Squamous Cell
dc.subjectLung Neoplasms
dc.subjectHistone-Lysine N-Methyltransferase
dc.subjectCarrier Proteins
dc.subjectNuclear Proteins
dc.subjectRepressor Proteins
dc.subjectCell Proliferation
dc.subjectEpigenesis, Genetic
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectProtein Binding
dc.subjectOncogenes
dc.subjectSOXB1 Transcription Factors
dc.subjectGene Knockdown Techniques
dc.subjectGenetic Loci
dc.titleBCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous carcinoma.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2018
prism.publicationNameNat Commun
prism.startingPage3327
prism.volume9
dc.identifier.doi10.17863/CAM.27863
dcterms.dateAccepted2018-07-09
rioxxterms.versionofrecord10.1038/s41467-018-05790-5
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-08-20
dc.contributor.orcidHadi, Fazal [0000-0003-3553-817X]
dc.contributor.orcidBach, Karsten [0000-0003-3622-1115]
dc.contributor.orcidSantolla, Maria-Francesca [0000-0002-4838-5953]
dc.contributor.orcidLadds, Graham [0000-0001-7320-9612]
dc.contributor.orcidLiu, Pentao [0000-0001-5774-9678]
dc.contributor.orcidEvan, Gerard [0000-0003-0412-1216]
dc.contributor.orcidMcCaughan, Frank [0000-0002-8012-7524]
dc.contributor.orcidLee, Joo [0000-0002-7364-6422]
dc.contributor.orcidKhaled, Walid [0000-0001-9068-5776]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Review
pubs.funder-project-idCancer Research UK (17348)
pubs.funder-project-idCancer Research UK (25850)
pubs.funder-project-idIsaac Newton Trust (16.38(c))
pubs.funder-project-idNational Centre for the Replacement Refinement and Reduction of Animals in Research (NC/N002369/1)
pubs.funder-project-idCancer Research UK (19013)
pubs.funder-project-idEuropean Research Council (679411)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/M00015X/2)
pubs.funder-project-idMedical Research Council (MC_PC_12009)
cam.issuedOnline2018-08-20
rioxxterms.freetoread.startdate2019-08-20


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