The Role of Cdk5 in Neuroendocrine Thyroid Cancer

Academic Article

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. © 2013 Elsevier Inc.
  • Digital Object Identifier (doi)

    Pubmed Id

  • 23490859
  • Author List

  • Pozo K; Castro-Rivera E; Tan C; Plattner F; Schwach G; Siegl V; Meyer D; Guo A; Gundara J; Mettlach G
  • Start Page

  • 499
  • End Page

  • 511
  • Volume

  • 24
  • Issue

  • 4