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dc.contributor.authorFrancis, JC
dc.contributor.authorCapper, A
dc.contributor.authorNing, J
dc.contributor.authorKnight, E
dc.contributor.authorde Bono, J
dc.contributor.authorSwain, A
dc.date.accessioned2019-07-17T09:07:31Z
dc.date.issued2018-01-10
dc.identifier.citationOncotarget, 2018, 9 (7), pp. 7604 - 7615
dc.identifier.issn1949-2553
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3292
dc.identifier.eissn1949-2553en_US
dc.identifier.doi10.18632/oncotarget.24123en_US
dc.description.abstractAggressive lethal prostate cancer is characterised by tumour invasion, metastasis and androgen resistance. Understanding the mechanisms by which localised disease progresses to advanced lethal stages is key to the development of effective therapies. Here we have identified a novel role for the transcription factor, SOX9, as a driver of aggressive invasive prostate cancer. Using genetically modified mouse models, we show that increased <i>Sox9</i> expression in the prostate epithelia of animals with <i>Pten</i> loss leads to a highly invasive phenotype and metastasis. In depth analysis of these mice and related <i>in vitro</i> models reveals that SOX9 acts a key regulator of various processes that together promote tumour progression. We show that this factor promotes cell lineage plasticity with cells acquiring properties of basal stem cells and an increase in proliferation. In addition, increased SOX9 leads to changes in cytoskeleton and adhesion, deposition of extracellular matrix and epithelia to mesenchyme transition, properties of highly invasive cells. Analysis of castrated mice showed that the invasive phenotype driven by SOX9 is independent of androgen levels. Our study has identified a novel driver of prostate cancer progression and highlighted the cellular and molecular processes that are regulated by <i>Sox9</i> to achieve invasive disease.
dc.formatElectronic-eCollection
dc.format.extent7604 - 7615
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.title<i>SOX9</i> is a driver of aggressive prostate cancer by promoting invasion, cell fate and cytoskeleton alterations and epithelial to mesenchymal transition.
dc.typeJournal Article
dcterms.dateAccepted2017-07-03
rioxxterms.versionofrecord10.18632/oncotarget.24123
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-01-10en_US
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfOncotarget
pubs.issue7
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Development & Cancer
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Development & Cancer
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Development & Cancer
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Development & Cancer
pubs.publication-statusPublished
pubs.volume9en_US
pubs.embargo.termsNot known
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
icr.researchteamDevelopment & Canceren_US
dc.contributor.icrauthorSwain, Amandaen
dc.contributor.icrauthorDe Bono, Johannen


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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/