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dc.contributor.authorSandsmark, Elise
dc.contributor.authorHansen, Ailin Falkmo
dc.contributor.authorSelnæs, Kirsten Margrete
dc.contributor.authorBertilsson, Helena
dc.contributor.authorBofin, Anna M.
dc.contributor.authorWright, Alan J.
dc.contributor.authorViset, Trond
dc.contributor.authorRichardsen, Elin
dc.contributor.authorDrabløs, Finn Sverre
dc.contributor.authorBathen, Tone Frost
dc.contributor.authorTessem, May-Britt
dc.contributor.authorRye, Morten Beck
dc.date.accessioned2017-01-24T08:06:21Z
dc.date.available2017-01-24T08:06:21Z
dc.date.issued2016-12-24
dc.description.abstractActivation of the Canonical Wnt pathway (CWP) has been linked to advanced and metastatic prostate cancer, whereas the Wnt5a-induced non-canonical Wnt pathway (NCWP) has been associated with both good and poor prognosis. A newly discovered NCWP, Wnt5/Fzd2, has been shown to induce epithelial-to-mesenchymal transition (EMT) in cancers, but has not been investigated in prostate cancer. The aim of this study was to investigate if the CWP and NCWP, in combination with EMT, are associated with metabolic alterations, aggressive disease and biochemical recurrence in prostate cancer. An initial analysis was performed using integrated transcriptomics, ex vivo and in vivo metabolomics, and histopathology of prostatectomy samples (n=129), combined with at least five-year follow-up. This analysis detected increased activation of NCWP through Wnt5a/ Fzd2 as the most common mode of Wnt activation in prostate cancer. This activation was associated with increased expression of EMT markers and higher Gleason score. The transcriptional association between NCWP and EMT was confirmed in five other publicly available patient cohorts (1519 samples in total). A novel gene expression signature of concordant activation of NCWP and EMT (NCWP-EMT) was developed, and this signature was significantly associated with metastasis and shown to be a significant predictor of biochemical recurrence. The NCWP-EMT signature was also associated with decreased concentrations of the metabolites citrate and spermine, which have previously been linked to aggressive prostate cancer. Our results demonstrate the importance of NCWP and EMT in prostate cancer aggressiveness, suggest a novel gene signature for improved risk stratification, and give new molecular insight.en_US
dc.descriptionThis article is also available at <a href="10.18632/oncotarget.14161">10.18632/oncotarget.14161</a><br> This is an article under the terms of the <a href="https://creativecommons.org/licenses/by/3.0/">Creative Commons Attribution 3.0 License</a>, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.en_US
dc.identifier.citationOncoTarget 2016:1-15en_US
dc.identifier.cristinIDFRIDAID 1418961
dc.identifier.doi10.18632/oncotarget.14161
dc.identifier.issn1949-2553
dc.identifier.urihttps://hdl.handle.net/10037/10187
dc.language.isoengen_US
dc.publisherImpact Journalsen_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762en_US
dc.titleA novel non-canonical Wnt signature for prostate cancer aggressivenessen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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