The Role of Cdk5 in Neuroendocrine Thyroid Cancer

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• 作者：Karine Pozo ; 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 ; et al.
• 刊名：Cancer Cell
• 出版年：2013
• 出版时间：14 October, 2013
• 年：2013
• 卷：24
• 期：4
• 页码：499-511
• 全文大小：4057 K

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class=""h3"">Summary

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.