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dc.contributor.authorAl-Lamki, Rafia S.
dc.contributor.authorHudson, Nicholas J.
dc.contributor.authorBradley, John R.
dc.contributor.authorWarren, Anne Y.
dc.contributor.authorEisen, Tim
dc.contributor.authorWelsh, Sarah J.
dc.contributor.authorRiddick, Antony C. P.
dc.contributor.authorO'Mahony, Fiach C.
dc.contributor.authorTurnbull, Arran
dc.contributor.authorPowles, Thomas
dc.contributor.authorSCOTRRCC Collaborative
dc.contributor.authorReverter, Antonio
dc.contributor.authorHarrison, David James
dc.contributor.authorStewart, Grant D.
dc.date.accessioned2020-04-07T14:30:01Z
dc.date.available2020-04-07T14:30:01Z
dc.date.issued2020-04-07
dc.identifier.citationAl-Lamki , R S , Hudson , N J , Bradley , J R , Warren , A Y , Eisen , T , Welsh , S J , Riddick , A C P , O'Mahony , F C , Turnbull , A , Powles , T , SCOTRRCC Collaborative , Reverter , A , Harrison , D J & Stewart , G D 2020 , ' The efficacy of sunitinib treatment of renal cancer is associated with the protein PHAX in vitro ' , Biology , vol. 9 , no. 4 , 74 . https://doi.org/10.3390/biology9040074en
dc.identifier.issn2079-7737
dc.identifier.otherPURE: 267188413
dc.identifier.otherPURE UUID: 706ef51a-c2b9-4c1d-969a-7a03e92a600a
dc.identifier.otherORCID: /0000-0001-9041-9988/work/71955437
dc.identifier.otherScopus: 85083783276
dc.identifier.otherWOS: 000533889200009
dc.identifier.urihttp://hdl.handle.net/10023/19763
dc.descriptionThis work was supported by: Chief Scientist Office, Scotland (grant number ETM37 to G.D.S. and D.J.H.), Cancer Research UK (Experimental Cancer Medicine Centre; CRUK Grant C505/A7328) (to D.J.H.), Cancer Research UK (Experimental Cancer Medicine Centre (to T.P.), Medical Research Council (to D.J.H.), Renal Cancer Research Fund (to G.D.S. and D.J.H.), Kidney Cancer Scotland (to G.D.S.), NIHR Cambridge Biomedical Research Centre, and an educational grant from Pfizer (to T.P.).en
dc.description.abstractAnti-angiogenic agents, such as the multi-tyrosine kinase inhibitor sunitinib, are key first line therapies for metastatic clear cell renal cell carcinoma (ccRCC), but their mechanism of action is not fully understood. Here, we take steps towards validating a computational prediction based on differential transcriptome network analysis that phosphorylated adapter RNA export protein (PHAX) is associated with sunitinib drug treatment. The regulatory impact factor differential network algorithm run on patient tissue samples suggests PHAX is likely an important regulator through changes in genome-wide network connectivity. Immunofluorescence staining of patient tumours showed strong localisation of PHAX to the microvasculature consistent with the anti-angiogenic effect of sunitinib. In normal kidney tissue, PHAX protein abundance was low but increased with tumour grade (G1 vs. G3/4; p < 0.01), consistent with a possible role in cancer progression. In organ culture, ccRCC cells had higher levels of PHAX protein expression than normal kidney cells, and sunitinib increased PHAX protein expression in a dose dependent manner (untreated vs. 100 µM; p < 0.05). PHAX knockdown in a ccRCC organ culture model impacted the ability of sunitinib to cause cancer cell death (p < 0.0001 untreated vs. treated), suggesting a role for PHAX in mediating the efficacy of sunitinib.
dc.format.extent21
dc.language.isoeng
dc.relation.ispartofBiologyen
dc.subjectRenal canceren
dc.subjectKidney canceren
dc.subjectSunitiniben
dc.subjectPHAXen
dc.subjectOrgan cultureen
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectDASen
dc.subject.lccRC0254en
dc.titleThe efficacy of sunitinib treatment of renal cancer is associated with the protein PHAX in vitroen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.Sir James Mackenzie Institute for Early Diagnosisen
dc.contributor.institutionUniversity of St Andrews.Cellular Medicine Divisionen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.identifier.doihttps://doi.org/10.3390/biology9040074
dc.description.statusPeer revieweden
dc.identifier.urlhttps://www.mdpi.com/2079-7737/9/4/74en


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