Inhibition of YAP/TAZ-driven TEAD activity prevents growth of NF2-null schwannoma and meningioma
dc.contributor.author | Laraba, Liyam | |
dc.contributor.author | Hillson, L | |
dc.contributor.author | de Guibert, JG | |
dc.contributor.author | Hewitt, A | |
dc.contributor.author | Jaques, MR | |
dc.contributor.author | Tang, TT | |
dc.contributor.author | Post, L | |
dc.contributor.author | Ercolano, E | |
dc.contributor.author | Rai, G | |
dc.contributor.author | Yang, SM | |
dc.contributor.author | Jagger, DJ | |
dc.contributor.author | Woznica, W | |
dc.contributor.author | Edwards, P | |
dc.contributor.author | Shivane, AG | |
dc.contributor.author | Hanemann, Clemens Oliver | |
dc.contributor.author | Parkinson, David | |
dc.date.accessioned | 2022-10-31T15:17:35Z | |
dc.date.issued | 2022-09-23 | |
dc.identifier.issn | 1460-2156 | |
dc.identifier.issn | 1460-2156 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/19801 | |
dc.description.abstract |
Schwannoma tumours typically arise on the 8th 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 8th 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 pre-clinical 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.extent | 1697-1713 | |
dc.format.medium | ||
dc.language | en | |
dc.language.iso | eng | |
dc.publisher | Oxford University Press | |
dc.subject | schwannoma | |
dc.subject | meningioma | |
dc.subject | Merlin | |
dc.subject | Hippo pathway | |
dc.subject | TEAD proteins | |
dc.title | Inhibition of YAP/TAZ-driven TEAD activity prevents growth of NF2-null schwannoma and meningioma | |
dc.type | journal-article | |
dc.type | Journal Article | |
dc.type | Research Support, Non-U.S. Gov't | |
plymouth.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000898261800001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008 | |
plymouth.issue | 4 | |
plymouth.volume | 146 | |
plymouth.publication-status | Published | |
plymouth.journal | Brain | |
dc.identifier.doi | 10.1093/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.place | England | |
dcterms.dateAccepted | 2022-09-08 | |
dc.rights.embargodate | 2022-11-1 | |
dc.identifier.eissn | 1460-2156 | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.1093/brain/awac342 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2022-09-23 | |
rioxxterms.type | Journal Article/Review |