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dc.contributor.authorWarren, Anne
dc.contributor.authorMassie, Charles
dc.contributor.authorWatt, Kate
dc.contributor.authorLuko, Katarina
dc.contributor.authorOrafidiya, Folake
dc.contributor.authorSelth, Luke A
dc.contributor.authorMohammed, Hisham
dc.contributor.authorChohan, Brinder S
dc.contributor.authorMenon, Suraj
dc.contributor.authorBaridi, Ajoeb
dc.contributor.authorZhao, Wanfeng
dc.contributor.authorEscriu, Carles
dc.contributor.authorPungsrinont, Thanakorn
dc.contributor.authorD'Santos, Clive
dc.contributor.authorYang, Xiaoping
dc.contributor.authorTaylor, Chris
dc.contributor.authorQureshi, Arham
dc.contributor.authorZecchini, Vincent R
dc.contributor.authorShaw, Greg L
dc.contributor.authorDehm, Scott M
dc.contributor.authorMills, Ian G
dc.contributor.authorCarroll, Jason
dc.contributor.authorTilley, Wayne D
dc.contributor.authorMcEwan, Iain J
dc.contributor.authorBaniahmad, Aria
dc.contributor.authorNeal, David E
dc.contributor.authorAsim, Mohammad
dc.date.accessioned2018-11-17T00:30:24Z
dc.date.available2018-11-17T00:30:24Z
dc.date.issued2019-02
dc.identifier.issn0950-9232
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285330
dc.description.abstractElucidation of mechanisms underlying the increased androgen receptor (AR) activity and subsequent development of aggressive prostate cancer (PrCa) is pivotal in developing new therapies. Using a systems biology approach, we interrogated the AR-regulated proteome and identified PDZ binding kinase (PBK) as a novel AR-regulated protein that regulates full-length AR and AR variants (ARVs) activity in PrCa. PBK overexpression in aggressive PrCa is associated with early biochemical relapse and poor clinical outcome. In addition to its carboxy terminus ligand-binding domain, PBK directly interacts with the amino terminus transactivation domain of the AR to stabilise it thereby leading to increased AR protein expression observed in PrCa. Transcriptome sequencing revealed that PBK is a mediator of global AR signalling with key roles in regulating tumour invasion and metastasis. PBK inhibition decreased growth of PrCa cell lines and clinical specimen cultured ex vivo. We uncovered a novel interplay between AR and PBK that results in increased AR and ARVs expression that executes AR-mediated growth and progression of PrCa, with implications for the development of PBK inhibitors for the treatment of aggressive PrCa.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCell Line, Tumor
dc.subjectHumans
dc.subjectProstatic Neoplasms
dc.subjectNeoplasm Invasiveness
dc.subjectNeoplasm Metastasis
dc.subjectMitogen-Activated Protein Kinase Kinases
dc.subjectNeoplasm Proteins
dc.subjectReceptors, Androgen
dc.subjectProtein Kinase Inhibitors
dc.subjectSignal Transduction
dc.subjectGene Expression Regulation
dc.subjectMale
dc.titleA reciprocal feedback between the PDZ binding kinase and androgen receptor drives prostate cancer.
dc.typeArticle
prism.endingPage1150
prism.issueIdentifier7
prism.publicationDate2019
prism.publicationNameOncogene
prism.startingPage1136
prism.volume38
dc.identifier.doi10.17863/CAM.27347
dcterms.dateAccepted2018-08-16
rioxxterms.versionofrecord10.1038/s41388-018-0501-z
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-02
dc.contributor.orcidWarren, Anne [0000-0002-1170-7867]
dc.contributor.orcidMassie, Charles [0000-0003-2314-4843]
dc.contributor.orcidDehm, Scott M [0000-0002-7827-5579]
dc.contributor.orcidCarroll, Jason [0000-0003-3643-0080]
dc.identifier.eissn1476-5594
rioxxterms.typeJournal Article/Review
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (A25117)
pubs.funder-project-idCancer Research UK (C14303/A17197)
cam.issuedOnline2018-09-20


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International