| Literature DB >> 24135281 |
Karine Pozo1, Emely Castro-Rivera, Chunfeng Tan, Florian Plattner, Gert Schwach, Veronika Siegl, Douglas Meyer, Ailan Guo, Justin Gundara, Gabriel Mettlach, Edmond Richer, Jonathan A Guevara, Li Ning, Anjali Gupta, Guiyang Hao, Li-Huei Tsai, Xiankai Sun, Pietro Antich, Stanley Sidhu, Bruce G Robinson, Herbert Chen, Fiemu E Nwariaku, Roswitha Pfragner, James A Richardson, James A Bibb.
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.Entities:
Mesh：
Substances：
Year: 2013 PMID： 24135281 PMCID： PMC3849320 DOI： 10.1016/j.ccr.2013.08.027
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743