Cyclin-dependent kinase 5 activity controls cell motility and metastatic potential of prostate cancer cells
Cyclin-dependent kinase 5 activity controls cell motility and metastatic potential of prostate cancer cells
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DOI：
10.1158/0008-5472.can-05-3048
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发表时间：
2006-08-01
期刊：
影响因子：
11.2
通讯作者：
Nelkin, Barry D.
中科院分区：
文献类型：
--
作者：
Strock, Christopher J.;Park, Jong-In;Nelkin, Barry D.
我们在此表明，细胞周期蛋白依赖性激酶5（CDK5），一种已知的神经元发育过程中迁移的调节因子，在前列腺癌的运动性和转移中发挥重要作用。P35是CDK5的一种激活剂，可指示其活性，它在一组人类和大鼠前列腺癌细胞系中表达，并且在我们所检测的87.5%的人类转移性前列腺癌中也有表达。用显性负性CDK5构建体、小干扰RNA或罗斯科维汀阻断CDK5活性，会导致微管细胞骨架发生变化、细胞极性丧失以及运动性丧失。在高转移性邓宁AT6.3前列腺癌细胞系中表达显性负性CDK5也会极大地削弱其侵袭能力。CDK5活性对体内自发转移很重要；表达显性负性CDK5的AT6.3细胞的异种移植物，其肺转移数量不到表达空载体的AT6.3细胞的四分之一。这些结果表明，CDK5活性控制着前列腺癌中的细胞运动性和转移潜能。
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.