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dc.contributor.authorMitchell, Ellen
dc.contributor.authorMellor, Charlotte E. L.
dc.contributor.authorPurba, Talveen S.; orcid: 0000-0003-3735-7735; email: talveen.purba@manchester.ac.uk
dc.date.accessioned2021-09-17T15:14:33Z
dc.date.available2021-09-17T15:14:33Z
dc.date.issued2020-09-17
dc.date.submitted2020-05-22
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/625880/13008_2020_Article_67_nlm.xml?sequence=2
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/625880/13008_2020_Article_67.pdf?sequence=3
dc.identifier.citationCell Division, volume 15, issue 1, page 11
dc.identifier.urihttp://hdl.handle.net/10034/625880
dc.descriptionFrom Springer Nature via Jisc Publications Router
dc.descriptionHistory: received 2020-05-22, registration 2020-09-03, accepted 2020-09-03, pub-electronic 2020-09-17, online 2020-09-17, collection 2020-12
dc.descriptionPublication status: Published
dc.descriptionFunder: Manchester Biomedical Research Centre; doi: http://dx.doi.org/10.13039/100014653
dc.description.abstractAbstract: Background: XMU-MP-1 is an inhibitor of the Hippo pathway kinases MST1/2 and has been shown to promote the downstream activation of the pro-proliferative, pro-regenerative and anti-apoptotic transcriptional regulator YAP1. We tested whether XMU-MP-1 can activate YAP1 in a model human mini-organ, namely the hair follicle, to determine whether it can be pharmacologically exploited to promote regeneration in the hair follicle as a novel strategy to treat pathological hair loss disorders. Results: XMU-MP-1 treatment inhibited MOB1 phosphorylation but did not increase active YAP1 in the hair follicle. Rather than promote proliferation, XMU-MP-1 serendipitously decreased the number of Ki-67+, EdU+ and phospho histone H3+ hair matrix keratinocytes and antagonised the cytotoxic effects of paclitaxel. Conclusions: XMU-MP-1 perturbs epithelial cell cycle progression in a model human mini-organ. This may arise as an off-target effect, especially when XMU-MP-1 has been described to strongly inhibit 21 additional kinases beyond MST1/2. Therefore, whilst these effects may be dependent on tissue context, researchers should exercise caution when interpreting the effects of XMU-MP-1, especially in tissues with actively proliferating cell populations.
dc.languageen
dc.publisherBioMed Central
dc.rightsLicence for this article: http://creativecommons.org/licenses/by/4.0/
dc.sourceeissn: 1747-1028
dc.subjectShort Report
dc.subjectXMU-MP-1
dc.subjectHippo
dc.subjectYAP1
dc.subjectCell cycle
dc.subjectProliferation
dc.subjectHair follicle
dc.subjectMST1/2
dc.subjectAurora B
dc.subjectChemotherapy
dc.subjectAlopecia
dc.titleXMU-MP-1 induces growth arrest in a model human mini-organ and antagonises cell cycle-dependent paclitaxel cytotoxicity
dc.typearticle
dc.date.updated2021-09-17T15:14:33Z
dc.date.accepted2020-09-03


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