The Role of Cdk5 in Neuroendocrine Thyroid Cancer
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Tsai_The Role of Cdk5.pdf
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4.7 MB
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Author(s)
Pozo, Karine
Castro-Rivera, Emely
Tan, Chunfeng
Plattner, Florian
Schwach, Gert
Siegl, Veronika
Meyer, Douglas
Guo, Ailan
Gundara, Justin
Mettlach, Gabriel
Date Issued
October 2013
Journal
Cancer Cell
Publisher
Elsevier
Citation
Pozo, 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.
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.ccr.2013.08.027
