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dc.contributor.authorShaikh, Mushfiq H
dc.contributor.authorIdris, Adi
dc.contributor.authorJohnson, Newell W
dc.contributor.authorFallaha, Sora
dc.contributor.authorClarke, Daniel TW
dc.contributor.authorMartin, David
dc.contributor.authorMorgan, Iain M
dc.contributor.authorGabrielli, Brian
dc.contributor.authorMcMillan, Nigel AJ
dc.date.accessioned2019-05-29T12:39:14Z
dc.date.available2019-05-29T12:39:14Z
dc.date.issued2018
dc.identifier.issn1368-8375
dc.identifier.doi10.1016/j.oraloncology.2018.09.006
dc.identifier.urihttp://hdl.handle.net/10072/381275
dc.description.abstractObjectives: Human papilloma virus (HPV) is the main culprit in cancers of the cervix, penis, anus, skin, eye and head and neck. Current treatments for HPV cancers have not altered survival outcomes for 30 years and there is a significant lack of targeted therapeutic agents in the management of advanced HPV-related HNSCC. Here we show that survival and maintenance of HPV-positive HNC cells relies on the continuous expression of the major HPV oncogene, E7, and that Aurora kinases are critical for survival of high-risk HPV-positive HNC cells. Materials and methods: To assess the role of HPV E7 on HNC cell survival, RNA interference (RNAi) of the E7 gene was initially performed. Using an Aurora kinase inhibitor, Alisertib, the role of Aurora kinases in the carcinogenesis of HPV E7 positive HNC tumour lines was then investigated. An in vivo HNC xenograft model was also utilised to assess loss of tumour volume in response to RNAi E7 gene silencing and Alisertib treatment. Results: RNAi silencing of the HPV E7 gene inhibited the growth of HPV-positive HNC cells and in vivo tumour load. We show that HPV E7 oncogene expression confers sensitivity to Alisertib on HNC cells where Alisertib-mediated loss in in vitro cell viability and in vivo tumour load is dependent on E7 expression. Moreover, Aurora kinase inhibition induced degradation of MCL-1 in HPV E7-expressing HNC cells. Conclusion: Overall, we show that Aurora kinases are a novel therapeutic target for HPV-positive HNCs. It might be feasible to combine Aurora kinase and MCL-1 inhibitors for future HNC therapies.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.publisher.placeUnited Kingdom
dc.relation.ispartofpagefrom105
dc.relation.ispartofpageto112
dc.relation.ispartofjournalOral Oncology
dc.relation.ispartofvolume86
dc.subject.fieldofresearchDentistry
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchCancer cell biology
dc.subject.fieldofresearchHealth services and systems
dc.subject.fieldofresearchPublic health
dc.subject.fieldofresearchcode3203
dc.subject.fieldofresearchcode3211
dc.subject.fieldofresearchcode321101
dc.subject.fieldofresearchcode4203
dc.subject.fieldofresearchcode4206
dc.titleAurora kinases are a novel therapeutic target for HPV-positive head and neck cancers
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyGriffith Health, School of Dentistry and Oral Health
gro.hasfulltextNo Full Text
gro.griffith.authorMcMillan, Nigel
gro.griffith.authorJohnson, Newell W.


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