@article{3d854a0af46741258d7797b4b32e8edc,
title = "The Role of Cdk5 in Neuroendocrine Thyroid Cancer",
abstract = "Medullary 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.",
author = "Karine Pozo and Emely Castro-Rivera and Chunfeng Tan and Florian Plattner and Gert Schwach and Veronika Siegl and Douglas Meyer and Ailan Guo and Justin Gundara and Gabriel Mettlach and Edmond Richer and Guevara, {Jonathan A.} and Li Ning and Anjali Gupta and Guiyang Hao and Tsai, {Li Huei} and Xiankai Sun and Pietro Antich and Stanley Sidhu and Robinson, {Bruce G.} and Herbert Chen and Nwariaku, {Fiemu E.} and Roswitha Pfragner and Richardson, {James A.} and Bibb, {James A.}",
note = "Funding Information: We thank G. Cote for MEN2A and control thyroid lysates; E. Knudsen for NDF cells and helpful advice; E. Nestler for NSE-Tta mice; K. Richter and L. Lau (Pfizer) for CP681301; F. Gillardon (Boehringer Ingelheim) for indolinone A; L. Meijer for roscovitine; and S. Hisanaga for the kinase-dead Cdk5 construct. We thank J. Shelton for histopathology advice; I. Mitchell, T. Singh, T. Crone, and L. O{\textquoteright}Connor for technical assistance; and A. Hillmann for reading the manuscript. This research was supported by a North American Neuroendocrine Tumor Society fellowship (to K.P.) and U.S. National Institutes of Health Grants to L.H.T. (NS051874), H.C. (CA121115 and CA109053), F.E.N. (GM067674), and J.A.B. (MH79710, MH083711, DA016672, DA033485, and NS073855); the Howard Hughes Medical Institute (to L.H.T.); and American Cancer Society MEN2 Thyroid Cancer Consortium research grants (RSGM-11-182-01 and RPM-11-080-01 to H.C. and RSGM-11-190-01 to J.A.B.). ",
year = "2013",
month = oct,
day = "14",
doi = "10.1016/j.ccr.2013.08.027",
language = "English (US)",
volume = "24",
pages = "499--511",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}