Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Pozo, K; Castro-Rivera, E; Tan, C; Plattner, F; Schwach, G; Siegl, V; Meyer, D; Guo, A; Gundara, J; Mettlach, G; Richer, E; Guevara, JA; Ning, L; Gupta, A; Hao, G; Tsai, LH; Sun, X; Antich, P; Sidhu, S; Robinson, BG; Chen, H; Nwariaku, FE; Pfragner, R; Richardson, JA; Bibb, JA.
The role of Cdk5 in neuroendocrine thyroid cancer.
Cancer Cell. 2013; 24(4):499-511
Doi: 10.1016/j.ccr.2013.08.027
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- Co-Autor*innen der Med Uni Graz
- Pfragner Roswitha
- Schwach Gert
- Siegl Veronika
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Carcinoma, Medullary - metabolism
- Carcinoma, Neuroendocrine - metabolism
- Cell Line, Tumor -
- Cell Proliferation -
- Cell Survival -
- Cyclin-Dependent Kinase 5 - metabolism
- Disease Progression -
- Gene Expression Regulation, Neoplastic -
- Humans -
- Mice -
- Mice, Transgenic -
- Phosphorylation -
- Retinoblastoma Protein - metabolism
- Signal Transduction -
- Thyroid Neoplasms - metabolism
- Time Factors -
- Transgenes -