000128918 001__ 128918
000128918 005__ 20240228143357.0
000128918 0247_ $$2doi$$a10.18632/oncotarget.6225
000128918 0247_ $$2pmid$$apmid:26506236
000128918 0247_ $$2pmc$$apmc:PMC4808008
000128918 037__ $$aDKFZ-2017-04931
000128918 041__ $$aeng
000128918 082__ $$a610
000128918 1001_ $$0P:(DE-He78)34ad9f967b71b1438cf5490a115c02d2$$aKnoll, Maximilian$$b0$$eFirst author$$udkfz
000128918 245__ $$aThe ribosomal protein S6 in renal cell carcinoma: functional relevance and potential as biomarker.
000128918 260__ $$a[S.l.]$$bImpact Journals LLC$$c2016
000128918 3367_ $$2DRIVER$$aarticle
000128918 3367_ $$2DataCite$$aOutput Types/Journal article
000128918 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1524470294_6386
000128918 3367_ $$2BibTeX$$aARTICLE
000128918 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000128918 3367_ $$00$$2EndNote$$aJournal Article
000128918 520__ $$aInhibitors of the mTOR pathway, such as everolimus, are promising compounds to treat patients with renal cell carcinomas (RCCs). However, the precise mechanisms of action are far from clear, and biomarkers predicting the response to mTOR inhibitors are still missing. Here, we provide evidence that in RCCs the rpS6 protein is the major mediator of anti-tumoral effects exerted by everolimus. Inhibition of mTOR signaling results in substantially decreased clonogenicity and proliferation of RCC cells, but did not significantly induce apoptosis. Everolimus effectively blocked protein biosynthesis both in vitro and in a novel ex vivo tissue slice model using fresh vital human RCC tissue. Compared to other components of the mTOR pathway, phosphorylation of rpS6 was most effectively downregulated by everolimus. Importantly, siRNA-mediated downregulation of rpS6, but not of 4ebp1 or p27, abolished the inhibitory effects of everolimus on proliferation and protein synthesis. Moreover, we analyzed the tissue expression of phosphorylated rpS6 (p-rpS6) and non-phosphorylated rpS6 in a large collection of patients with RCCs (n=598 and n=548, respectively). Expression of both proteins qualified as independent negative prognostic markers with a substantially shorter survival of patients with RCCs exhibiting high levels of rpS6 and p-rpS6. Taken together, our functional studies identified rpS6 as a main mediator of the anti-tumoral activity of Everolimus. Therefore, further (pre-)clinical evaluations of rpS6 as a predictive marker for everolimus-based treatment for RCC patients are warranted. Finally, the combined detection of phosphorylated and non-phosphorylated rpS6 could represent a robust prognostic marker to identify patients with high risk RCCs.
000128918 536__ $$0G:(DE-HGF)POF3-317$$a317 - Translational cancer research (POF3-317)$$cPOF3-317$$fPOF III$$x0
000128918 588__ $$aDataset connected to CrossRef, PubMed,
000128918 650_7 $$2NLM Chemicals$$aAntineoplastic Agents
000128918 650_7 $$2NLM Chemicals$$aBiomarkers, Tumor
000128918 650_7 $$2NLM Chemicals$$aRibosomal Protein S6
000128918 650_7 $$09HW64Q8G6G$$2NLM Chemicals$$aEverolimus
000128918 7001_ $$0P:(DE-HGF)0$$aMacher-Goeppinger, Stephan$$b1
000128918 7001_ $$0P:(DE-HGF)0$$aKopitz, Jürgen$$b2
000128918 7001_ $$aDuensing, Stefan$$b3
000128918 7001_ $$aPahernik, Sascha$$b4
000128918 7001_ $$aHohenfellner, Markus$$b5
000128918 7001_ $$aSchirmacher, Peter$$b6
000128918 7001_ $$0P:(DE-He78)6c54d919bb3371b6d7f277e2c6262a4a$$aRoth, Wilfried$$b7$$eLast author$$udkfz
000128918 773__ $$0PERI:(DE-600)2560162-3$$a10.18632/oncotarget.6225$$gVol. 7, no. 1, p. 418 - 432$$n1$$p418 - 432$$tOncoTarget$$v7$$x1949-2553$$y2016
000128918 909CO $$ooai:inrepo02.dkfz.de:128918$$pVDB
000128918 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)34ad9f967b71b1438cf5490a115c02d2$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ
000128918 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ
000128918 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ
000128918 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)6c54d919bb3371b6d7f277e2c6262a4a$$aDeutsches Krebsforschungszentrum$$b7$$kDKFZ
000128918 9131_ $$0G:(DE-HGF)POF3-317$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vTranslational cancer research$$x0
000128918 9141_ $$y2016
000128918 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bONCOTARGET : 2015
000128918 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000128918 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000128918 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000128918 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000128918 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000128918 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000128918 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000128918 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bONCOTARGET : 2015
000128918 9201_ $$0I:(DE-He78)G150-20160331$$kG150$$lMolekulare Tumorpathologie$$x0
000128918 9201_ $$0I:(DE-He78)G105-20160331$$kG105$$lGentherapie von Tumoren$$x1
000128918 980__ $$ajournal
000128918 980__ $$aVDB
000128918 980__ $$aI:(DE-He78)G150-20160331
000128918 980__ $$aI:(DE-He78)G105-20160331
000128918 980__ $$aUNRESTRICTED