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The Role of Cdk5 in Neuroendocrine Thyroid Cancer

dc.contributor.authorPozo, Karine
dc.contributor.authorCastro-Rivera, Emely
dc.contributor.authorTan, Chunfeng
dc.contributor.authorPlattner, Florian
dc.contributor.authorSchwach, Gert
dc.contributor.authorSiegl, Veronika
dc.contributor.authorMeyer, Douglas
dc.contributor.authorGuo, Ailan
dc.contributor.authorGundara, Justin
dc.contributor.authorMettlach, Gabriel
dc.contributor.authorRicher, Edmond
dc.contributor.authorGuevara, Jonathan A.
dc.contributor.authorNing, Li
dc.contributor.authorGupta, Anjali
dc.contributor.authorHao, Guiyang
dc.contributor.authorTsai, Li-Huei
dc.contributor.authorSun, Xiankai
dc.contributor.authorAntich, Pietro
dc.contributor.authorSidhu, Stanley
dc.contributor.authorRobinson, Bruce G.
dc.contributor.authorChen, Herbert
dc.contributor.authorNwariaku, Fiemu E.
dc.contributor.authorPfragner, Roswitha
dc.contributor.authorRichardson, James A.
dc.contributor.authorBibb, James A.
dc.date.accessioned2016-05-16T16:50:47Z
dc.date.available2016-05-16T16:50:47Z
dc.date.issued2013-10
dc.date.submitted2013-06
dc.identifier.issn15356108
dc.identifier.urihttp://hdl.handle.net/1721.1/102512
dc.description.abstractMedullary thyroid carcinoma (MTC) is a neuroendocrine cancer that originates from calcitonin-secreting parafollicular cells, or C cells. We found that Cdk5 and its cofactors p35 and p25 are highly expressed in human MTC and that Cdk5 activity promotes MTC proliferation. A conditional MTC mouse model was generated and corroborated the role of aberrant Cdk5 activation in MTC. C cell-specific overexpression of p25 caused rapid C cell hyperplasia leading to lethal MTC, which was arrested by repressing p25 overexpression. A comparative phosphoproteomic screen between proliferating and arrested MTC identified the retinoblastoma protein (Rb) as a crucial Cdk5 downstream target. Prevention of Rb phosphorylation at Ser807/Ser811 attenuated MTC proliferation. These findings implicate Cdk5 signaling via Rb as critical to MTC tumorigenesis and progression.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant NS051874)en_US
dc.description.sponsorshipHoward Hughes Medical Instituteen_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.ccr.2013.08.027en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleThe Role of Cdk5 in Neuroendocrine Thyroid Canceren_US
dc.typeArticleen_US
dc.identifier.citationPozo, Karine, Emely Castro-Rivera, Chunfeng Tan, Florian Plattner, Gert Schwach, Veronika Siegl, Douglas Meyer, et al. “The Role of Cdk5 in Neuroendocrine Thyroid Cancer.” Cancer Cell 24, no. 4 (October 2013): 499–511.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.departmentPicower Institute for Learning and Memoryen_US
dc.contributor.mitauthorTsai, Li-Hueien_US
dc.relation.journalCancer Cellen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsPozo, Karine; Castro-Rivera, Emely; Tan, Chunfeng; Plattner, Florian; Schwach, Gert; Siegl, Veronika; Meyer, Douglas; Guo, Ailan; Gundara, Justin; Mettlach, Gabriel; Richer, Edmond; Guevara, Jonathan A.; Ning, Li; Gupta, Anjali; Hao, Guiyang; Tsai, Li-Huei; Sun, Xiankai; Antich, Pietro; Sidhu, Stanley; Robinson, Bruce G.; Chen, Herbert; Nwariaku, Fiemu E.; Pfragner, Roswitha; Richardson, James A.; Bibb, James A.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0003-1262-0592
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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