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dc.contributor.authorShaik, Shavali
dc.contributor.authorNucera, Carmelo
dc.contributor.authorInuzuka, Hiroyuki
dc.contributor.authorGao, Daming
dc.contributor.authorGarnaas, Maija
dc.contributor.authorFrechette, Gregory Martin
dc.contributor.authorHarris, Lauren
dc.contributor.authorWan, Lixin
dc.contributor.authorFukushima, Hidefumi
dc.contributor.authorHusain, Amjad
dc.contributor.authorNose, Vania
dc.contributor.authorFadda, Guido
dc.contributor.authorSadow, Peter Mark
dc.contributor.authorGoessling, Wolfram
dc.contributor.authorNorth, Trista Elizabeth
dc.contributor.authorLawler, Jack William
dc.contributor.authorWei, Wenyi
dc.date.accessioned2013-05-07T16:00:58Z
dc.date.issued2012
dc.identifier.citationShaik, Shavali, Carmelo Nucera, Hiroyuki Inuzuka, Daming Gao, Maija Garnaas, Gregory Frechette, Lauren Harris, et al. 2012. SCF\(^{β-TRCP}\) suppresses angiogenesis and thyroid cancer cell migration by promoting ubiquitination and destruction of VEGF receptor 2. The Journal of Experimental Medicine 209(7): 1289-1307.en_US
dc.identifier.issn0022-1007en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10611735
dc.description.abstractThe incidence of human papillary thyroid cancer (PTC) is increasing and an aggressive subtype of this disease is resistant to treatment with vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor. VEGFR2 promotes angiogenesis by triggering endothelial cell proliferation and migration. However, the molecular mechanisms governing VEGFR2 stability in vivo remain unknown. Additionally, whether VEGFR2 influences PTC cell migration is not clear. We show that the ubiquitin E3 ligase SCF\(^{β-TRCP}\) promotes ubiquitination and destruction of VEGFR2 in a casein kinase I (CKI)–dependent manner. β-TRCP knockdown or CKI inhibition causes accumulation of VEGFR2, resulting in increased activity of signaling pathways downstream of VEGFR2. β-TRCP–depleted endothelial cells exhibit enhanced migration and angiogenesis in vitro. Furthermore, β-TRCP knockdown increased angiogenesis and vessel branching in zebrafish. Importantly, we found an inverse correlation between β-TRCP protein levels and angiogenesis in PTC. We also show that β-TRCP inhibits cell migration and decreases sensitivity to the VEGFR2 inhibitor sorafenib in poorly differentiated PTC cells. These results provide a new biomarker that may aid a rational use of tyrosine kinase inhibitors to treat refractory PTC.en_US
dc.language.isoen_USen_US
dc.publisherThe Rockefeller University Pressen_US
dc.relation.isversionofdoi:10.1084/jem.20112446en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405505/pdf/en_US
dash.licenseLAA
dc.titleSCF\(^{β-TRCP}\) Suppresses Angiogenesis and Thyroid Cancer Cell Migration by Promoting Ubiquitination and Destruction of VEGF Receptor 2en_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalThe Journal of Experimental Medicineen_US
dash.depositing.authorLawler, Jack William
dc.date.available2013-05-07T16:00:58Z
dc.identifier.doi10.1084/jem.20112446*
dash.authorsorderedfalse
dash.contributor.affiliatedFrechette, Gregory Martin
dash.contributor.affiliatedGao, Daming
dash.contributor.affiliatedHusain, Amjad
dash.contributor.affiliatedNorth, Trista
dash.contributor.affiliatedLawler, Jack
dash.contributor.affiliatedNose, Vania
dash.contributor.affiliatedNucera, Carmelo
dash.contributor.affiliatedGoessling, Wolfram
dash.contributor.affiliatedShaik, Shavali
dash.contributor.affiliatedWan, Lixin
dash.contributor.affiliatedSadow, Peter
dash.contributor.affiliatedInuzuka, Hiroyuki
dash.contributor.affiliatedWei, Wenyi


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