The role of Cdk5 in neuroendocrine thyroid cancer.
نویسندگان
چکیده
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.
منابع مشابه
Breaking Bad: how does a neuronal protein cause neuroendocrine cancer?
Medullary thyroid carcinomas (MTC) are slowgrowing tumors originating from neuroendocrine, parafollicular cells (C-cells) in the thyroid gland. Despite its low prevalence, MTC is one of the most deadly forms of thyroid cancers. Like other neuroendocrine cancers (e.g. pancreatic), MTC is often diagnosed at advanced stages at which surgical removal of the thyroid is no longer an effective treatme...
متن کاملDifferential expression of cell cycle regulators in CDK5-dependent medullary thyroid carcinoma tumorigenesis
Medullary thyroid carcinoma (MTC) is a neuroendocrine cancer of thyroid C-cells, for which few treatment options are available. We have recently reported a role for cyclin-dependent kinase 5 (CDK5) in MTC pathogenesis. We have generated a mouse model, in which MTC proliferation is induced upon conditional overexpression of the CDK5 activator, p25, in C-cells, and arrested by interrupting p25 ov...
متن کاملMedullary Thyroid Cancer: A Review
Thyroid cancer is a malignancy of the thyroid parenchymal cells. There are four main types of thyroid cancer: papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), anaplastic thyroid carcinoma (ATC), and Medullary thyroid carcinoma (MTC). Medullary thyroid cancer (MTC) is a rare neuroendocrine tumor of the thyroid gland derived from parafollicular C-cells that produce calcitonin (CT...
متن کاملGenetic and Epigenetic of Medullary Thyroid Cancer
Medullary thyroid carcinoma (MTC) is an infrequent calcitonin-producing neuroendocrine tumor that initiates from the parafollicular C cells of the thyroid gland. Several genetic and epigenetic alterations are collaterally responsible for medullary thyroid carcinogenesis. In this review article, we shed light on all the genetic and epigenetic hallmarks of MTC. From the genetic perspective, RET, ...
متن کاملAchaete-scute homologue-1 (ASH1) stimulates migration of lung cancer cells through Cdk5/p35 pathway
Our previous data suggested that the human basic helix-loop-helix transcription factor achaete-scute homologue-1 (hASH1) may stimulate both proliferation and migration in the lung. In the CNS, cyclin-dependent kinase 5 (Cdk5) and its activator p35 are important for neuronal migration that is regulated by basic helix-loop-helix transcription factors. Cdk5/p35 may also play a role in carcinogenes...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cancer cell
دوره 24 4 شماره
صفحات -
تاریخ انتشار 2013