| First Author | Pozo K | Year | 2013 |
| Journal | Cancer Cell | Volume | 24 |
| Issue | 4 | Pages | 499-511 |
| PubMed ID | 24135281 | Mgi Jnum | J:206200 |
| Mgi Id | MGI:5548063 | Doi | 10.1016/j.ccr.2013.08.027 |
| Citation | Pozo K, et al. (2013) The role of Cdk5 in neuroendocrine thyroid cancer. Cancer Cell 24(4):499-511 |
| abstractText | 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. |
