The Role of Cdk5 in Neuroendocrine Thyroid Cancer
- Pozo, 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.
DOIAbstract
SummaryMedullary 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 MT...
Add to ORKG