This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Strock, C. J. Articles by Nelkin, B. D. Search for Related Content PubMed PubMed Citation Articles by Strock, C. J. Articles by Nelkin, B. D.

Cyclin-Dependent Kinase 5 Activity Controls Cell Motility and Metastatic Potential of Prostate Cancer Cells

¹ Sidney Kimmel Comprehensive Cancer Center, Departments of ² Urology, ³ Pathology, and ⁴ Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland

Requests for reprints: Barry D. Nelkin, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, CRBI, Room 552, 1650 Orleans Street, Baltimore, MD 21231. Phone: 410-955-8506; Fax: 410-614-9884; E-mail: bnelkin{at}jhmi.edu.

We show here that cyclin-dependent kinase 5 (CDK5), a known regulator of migration in neuronal development, plays an important role in prostate cancer motility and metastasis. P35, an activator of CDK5 that is indicative of its activity, is expressed in a panel of human and rat prostate cancer cell lines, and is also expressed in 87.5% of the human metastatic prostate cancers we examined. Blocking of CDK5 activity with a dominant-negative CDK5 construct, small interfering RNA, or roscovitine resulted in changes in the microtubule cytoskeleton, loss of cellular polarity, and loss of motility. Expression of a dominant-negative CDK5 in the highly metastatic Dunning AT6.3 prostate cancer cell line also greatly impaired invasive capacity. CDK5 activity was important for spontaneous metastasis in vivo; xenografts of AT6.3 cells expressing dominant-negative CDK5 had less than one-fourth the number of lung metastases exhibited by AT6.3 cells expressing the empty vector. These results show that CDK5 activity controls cell motility and metastatic potential in prostate cancer. (Cancer Res 2006; 66(15): 7509-15) (Cancer Res 2006; 66(15): 7509-15)

This article has been cited by other articles:

				K.-H. Sun, Y. de Pablo, F. Vincent, E. O. Johnson, A. K. Chavers, and K. Shah Novel Genetic Tools Reveal Cdk5's Major Role in Golgi Fragmentation in Alzheimer's Disease Mol. Biol. Cell, July 1, 2008; 19(7): 3052 - 3069. [Abstract] [Full Text] [PDF]

				R. Liu, B. Tian, M. Gearing, S. Hunter, K. Ye, and Z. Mao Cdk5-mediated regulation of the PIKE-A-Akt pathway and glioblastoma cell invasion PNAS, May 27, 2008; 105(21): 7570 - 7575. [Abstract] [Full Text] [PDF]

				L. Liu, B. Schwartz, Y. Tsubota, E. Raines, H. Kiyokawa, K. Yonekawa, J. M. Harlan, and L. M. Schnapp Cyclin-Dependent Kinase Inhibitors Block Leukocyte Adhesion and Migration J. Immunol., February 1, 2008; 180(3): 1808 - 1817. [Abstract] [Full Text] [PDF]

				H. Lin, M.-C. Chen, C.-Y. Chiu, Y.-M. Song, and S.-Y. Lin Cdk5 Regulates STAT3 Activation and Cell Proliferation in Medullary Thyroid Carcinoma Cells J. Biol. Chem., February 2, 2007; 282(5): 2776 - 2784. [Abstract] [Full Text] [PDF]