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dc.contributor.authorAzzarelli, Roberta
dc.contributor.authorMcNally, Aoibheann
dc.contributor.authorDell’Amico, Claudia
dc.contributor.authorOnorati, Marco
dc.contributor.authorSimons, Benjamin
dc.contributor.authorPhilpott, Anna
dc.date.accessioned2022-02-11T17:40:26Z
dc.date.available2022-02-11T17:40:26Z
dc.date.issued2022-12
dc.date.submitted2021-09-24
dc.identifier.others41598-022-06248-x
dc.identifier.other6248
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/333926
dc.description.abstract<jats:title>Abstract</jats:title><jats:p>The growth of glioblastoma (GBM), one of the deadliest adult cancers, is fuelled by a subpopulation of stem/progenitor cells, which are thought to be the source of resistance and relapse after treatment. Re-engagement of a latent capacity of these cells to re-enter a trajectory resulting in cell differentiation is a potential new therapeutic approach for this devastating disease. ASCL1, a proneural transcription factor, plays a key role in normal brain development and is also expressed in a subset of GBM cells, but fails to engage a full differentiation programme in this context. Here, we investigated the barriers to ASCL1-driven differentiation in GBM stem cells. We see that ASCL1 is highly phosphorylated in GBM stem cells where its expression is compatible with cell proliferation. However, overexpression of a form of ASCL1 that cannot be phosphorylated on Serine–Proline sites drives GBM cells down a neuronal lineage and out of cell cycle more efficiently than its wild-type counterpart, an effect further enhanced by deletion of the inhibitor of differentiation ID2, indicating mechanisms to reverse the block to GBM cell differentiation.</jats:p>
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/67
dc.subject/631/80
dc.subject/631/136
dc.subject/631/532
dc.subjectarticle
dc.titleASCL1 phosphorylation and ID2 upregulation are roadblocks to glioblastoma stem cell differentiation
dc.typeArticle
dc.date.updated2022-02-11T17:40:25Z
prism.issueIdentifier1
prism.publicationNameScientific Reports
prism.volume12
dc.identifier.doi10.17863/CAM.81342
dcterms.dateAccepted2022-01-20
rioxxterms.versionofrecord10.1038/s41598-022-06248-x
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.identifier.eissn2045-2322
pubs.funder-project-idSociety for Developmental Biology ('Innovation Grant')
pubs.funder-project-idMinistero dell’Istruzione, dell’Università e della Ricerca ('Rita Levi Montalcini' program)
pubs.funder-project-idCancer Research UK (Studentship, A25636)
pubs.funder-project-idMinistero della Salute (GR-2018-12367290)
pubs.funder-project-idWellcome Trust (098357/Z/12/Z, 212253/Z/18/Z)
pubs.funder-project-idRoyal Society (RP\R1\180165)
cam.issuedOnline2022-02-11


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