000129046 001__ 129046 000129046 005__ 20240228143406.0 000129046 0247_ $$2doi$$a10.1158/0008-5472.CAN-16-1547 000129046 0247_ $$2pmid$$apmid:27496710 000129046 0247_ $$2pmc$$apmc:PMC5091083 000129046 0247_ $$2ISSN$$a0008-5472 000129046 0247_ $$2ISSN$$a0099-7013 000129046 0247_ $$2ISSN$$a0099-7374 000129046 0247_ $$2ISSN$$a1538-7445 000129046 0247_ $$2altmetric$$aaltmetric:10297953 000129046 037__ $$aDKFZ-2017-05051 000129046 041__ $$aeng 000129046 082__ $$a610 000129046 1001_ $$aLi, Peng$$b0 000129046 245__ $$aNestin Mediates Hedgehog Pathway Tumorigenesis. 000129046 260__ $$aPhiladelphia, Pa.$$bAACR$$c2016 000129046 3367_ $$2DRIVER$$aarticle 000129046 3367_ $$2DataCite$$aOutput Types/Journal article 000129046 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1524820878_12307 000129046 3367_ $$2BibTeX$$aARTICLE 000129046 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000129046 3367_ $$00$$2EndNote$$aJournal Article 000129046 520__ $$aThe intermediate filament protein Nestin serves as a biomarker for stem cells and has been used to identify subsets of cancer stem-like cells. However, the mechanistic contributions of Nestin to cancer pathogenesis are not understood. Here, we report that Nestin binds the hedgehog pathway transcription factor Gli3 to mediate the development of medulloblastomas of the hedgehog subtype. In a mouse model system, Nestin levels increased progressively during medulloblastoma formation, resulting in enhanced tumor growth. Conversely, loss of Nestin dramatically inhibited proliferation and promoted differentiation. Mechanistic investigations revealed that the tumor-promoting effects of Nestin were mediated by binding to Gli3, a zinc finger transcription factor that negatively regulates hedgehog signaling. Nestin binding to Gli3 blocked Gli3 phosphorylation and its subsequent proteolytic processing, thereby abrogating its ability to negatively regulate the hedgehog pathway. Our findings show how Nestin drives hedgehog pathway-driven cancers and uncover in Gli3 a therapeutic target to treat these malignancies. Cancer Res; 76(18); 5573-83. ©2016 AACR. 000129046 536__ $$0G:(DE-HGF)POF3-317$$a317 - Translational cancer research (POF3-317)$$cPOF3-317$$fPOF III$$x0 000129046 588__ $$aDataset connected to CrossRef, PubMed, 000129046 650_7 $$2NLM Chemicals$$aGli3 protein, mouse 000129046 650_7 $$2NLM Chemicals$$aHedgehog Proteins 000129046 650_7 $$2NLM Chemicals$$aKruppel-Like Transcription Factors 000129046 650_7 $$2NLM Chemicals$$aNerve Tissue Proteins 000129046 650_7 $$2NLM Chemicals$$aNes protein, mouse 000129046 650_7 $$2NLM Chemicals$$aNestin 000129046 7001_ $$aLee, Eric H$$b1 000129046 7001_ $$aDu, Fang$$b2 000129046 7001_ $$aGordon, Renata E$$b3 000129046 7001_ $$aYuelling, Larra W$$b4 000129046 7001_ $$aLiu, Yongqiang$$b5 000129046 7001_ $$aNg, Jessica M Y$$b6 000129046 7001_ $$aZhang, Hao$$b7 000129046 7001_ $$aWu, Jinhua$$b8 000129046 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b9$$udkfz 000129046 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b10$$udkfz 000129046 7001_ $$aCurran, Tom$$b11 000129046 7001_ $$aYang, Zeng-Jie$$b12 000129046 773__ $$0PERI:(DE-600)2036785-5$$a10.1158/0008-5472.CAN-16-1547$$gVol. 76, no. 18, p. 5573 - 5583$$n18$$p5573 - 5583$$tCancer research$$v76$$x1538-7445$$y2016 000129046 909CO $$ooai:inrepo02.dkfz.de:129046$$pVDB 000129046 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aDeutsches Krebsforschungszentrum$$b9$$kDKFZ 000129046 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aDeutsches Krebsforschungszentrum$$b10$$kDKFZ 000129046 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 000129046 9141_ $$y2016 000129046 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000129046 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bCANCER RES : 2015 000129046 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000129046 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000129046 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search 000129046 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC 000129046 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List 000129046 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index 000129046 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000129046 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000129046 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine 000129046 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences 000129046 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews 000129046 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bCANCER RES : 2015 000129046 9201_ $$0I:(DE-He78)G380-20160331$$kG380$$lKKE Neuropathologie$$x0 000129046 9201_ $$0I:(DE-He78)B062-20160331$$kB062$$lPädiatrische Neuroonkologie$$x1 000129046 9201_ $$0I:(DE-He78)L101-20160331$$kL101$$lDKTK Heidelberg$$x2 000129046 980__ $$ajournal 000129046 980__ $$aVDB 000129046 980__ $$aI:(DE-He78)G380-20160331 000129046 980__ $$aI:(DE-He78)B062-20160331 000129046 980__ $$aI:(DE-He78)L101-20160331 000129046 980__ $$aUNRESTRICTED