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dc.contributor.authorKucia-Tran, Justyna Aen
dc.contributor.authorTulkki, Valtterien
dc.contributor.authorSmith, Stephenen
dc.contributor.authorScarpini, Cinziaen
dc.contributor.authorHughes, Katherineen
dc.contributor.authorAraujo, Angela Men
dc.contributor.authorYan, Ka Yin Matthewen
dc.contributor.authorBotthof, Janen
dc.contributor.authorPérez-Gómez, Eduardoen
dc.contributor.authorQuintanilla, Miguelen
dc.contributor.authorCuschieri, Kateen
dc.contributor.authorCaffarel, Maria Men
dc.contributor.authorColeman, Nicholasen
dc.date.accessioned2016-06-23T14:39:58Z
dc.date.available2016-06-23T14:39:58Z
dc.date.issued2016en
dc.identifier.issn0007-0920
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/256462
dc.description.abstract$\textit{Background }$ Copy-number gain of the oncostatin-M receptor (OSMR) occurs frequently in cervical squamous cell carcinoma (SCC) and is associated with adverse clinical outcome. We previously showed that OSMR over-expression renders cervical SCC cells more sensitive to the major ligand oncostatin-M (OSM), which increases migration and invasion $\textit{in vitro}$. We hypothesised that a major contribution to this phenotype would come from epithelial-mesenchymal transition (EMT). $\textit{Methods }$ We performed a comprehensive integrated study, involving $\textit{in vitro}$ cell line studies, $\textit{in vivo}$ animal models and numerous clinical samples from a variety of anatomical sites. $\textit{Results }$ In independent sets of cervical, head/neck and lung SCC tissues, OSMR expression levels correlated with multiple EMT-associated phenotypic markers and transcription factors. OSM treatment of OSMR over-expressing cervical SCC cells produced consistent EMT changes and increased tumour sphere formation in suspension culture. In a mouse model, OSMR over-expressing SCC cells treated with OSM showed significant increases in lung colonisation. The biological effects of exogenous OSM were mirrored by highly significant adverse overall survival in cervical SCCs with OSMR over-expression (N=251). $\textit{Conclusions }$ OSM:OSMR interactions are able to induce EMT, increased cancer stem cell-like properties and enhanced lung colonisation in SCC cells. These changes are likely to contribute to the highly significant adverse outcome associated with OSMR over-expression in cervical SCCs.
dc.description.sponsorshipThis work was supported by Cancer Research UK (Programme Grant A13080).
dc.languageEnglishen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/
dc.subjectcervixen
dc.subjectsquamous cell carcinomaen
dc.subjectoncostatin-M receptoren
dc.subjectepithelial-mesenchymal transitionen
dc.subjectmetastasisen
dc.subjectSTAT3en
dc.titleOver-expression of the oncostatin-M receptor in cervical squamous cell carcinoma is associated with epithelial-mesenchymal transition and poor overall survivalen
dc.typeArticle
dc.description.versionThis is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Nature Publishing Group.en
prism.publicationDate2016en
prism.publicationNameBritish Journal of Canceren
dc.identifier.doi10.17863/CAM.408
dcterms.dateAccepted2016-05-26en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2016en
dc.contributor.orcidSmith, Stephen [0000-0001-7744-3238]
dc.contributor.orcidScarpini, Cinzia [0000-0003-4730-5197]
dc.contributor.orcidHughes, Katherine [0000-0002-3331-1249]
dc.identifier.eissn1532-1827
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MR/R001146/1)
cam.orpheus.successThu Jan 30 12:58:00 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution-NonCommercial-ShareAlike 4.0 International
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