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dc.contributor.authorParkinson, D
dc.date.accessioned2022-10-31T15:17:35Z
dc.date.issued2022-09-23
dc.identifier.issn1460-2156
dc.identifier.issn1460-2156
dc.identifier.urihttp://hdl.handle.net/10026.1/19801
dc.description.abstract

Schwannoma tumours typically arise on the eighth cranial nerve and are mostly caused by loss of the tumour suppressor Merlin (NF2). There are no approved chemotherapies for these tumours and the surgical removal of the tumour carries a high risk of damage to the eighth or other close cranial nerve tissue. New treatments for schwannoma and other NF2-null tumours such as meningioma are urgently required.

Using a combination of human primary tumour cells and mouse models of schwannoma, we have examined the role of the Hippo signalling pathway in driving tumour cell growth. Using both genetic ablation of the Hippo effectors YAP and TAZ as well as novel TEAD palmitoylation inhibitors, we show that Hippo signalling may be successfully targeted in vitro and in vivo to both block and, remarkably, regress schwannoma tumour growth. In particular, successful use of TEAD palmitoylation inhibitors in a preclinical mouse model of schwannoma points to their potential future clinical use. We also identify the cancer stem cell marker aldehyde dehydrogenase 1A1 (ALDH1A1) as a Hippo signalling target, driven by the TAZ protein in human and mouse NF2-null schwannoma cells, as well as in NF2-null meningioma cells, and examine the potential future role of this new target in halting schwannoma and meningioma tumour growth.

dc.format.extent1697-1713
dc.format.mediumPrint
dc.languageen
dc.language.isoeng
dc.publisherOxford University Press
dc.subjectschwannoma
dc.subjectmeningioma
dc.subjectMerlin
dc.subjectHippo pathway
dc.subjectTEAD proteins
dc.titleInhibition of YAP/TAZ-driven TEAD activity prevents growth of NF2-null schwannoma and meningioma
dc.typejournal-article
dc.typeArticle
plymouth.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/36148553
plymouth.issue4
plymouth.volume146
plymouth.publisher-urlhttp://dx.doi.org/10.1093/brain/awac342
plymouth.publication-statusPublished
plymouth.journalBrain
dc.identifier.doi10.1093/brain/awac342
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/Peninsula Medical School
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
plymouth.organisational-group/Plymouth/Users by role/Researchers in ResearchFish submission
dc.publisher.placeEngland
dcterms.dateAccepted2022-09-08
dc.rights.embargodate2022-11-8
dc.identifier.eissn1460-2156
dc.rights.embargoperiodNot known
rioxxterms.versionofrecord10.1093/brain/awac342
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2022-09-23
rioxxterms.typeJournal Article/Review


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