Department of Life Sciences, National Chung Hsing University, Taichung 40227, Taiwan.
Department of Urology, Chang Bing Show Chwan Memorial Hospital, Changhua 505, Taiwan.
Int J Mol Sci. 2019 Aug 9;20(16):3881. doi: 10.3390/ijms20163881.
Cyclin-dependent kinase 5 (CDK5) is a unique member of the cyclin-dependent kinase family. CDK5 is activated by binding with its regulatory proteins, mainly p35, and its activation is essential in the development of the central nervous system (CNS) and neurodegeneration. Recently, it has been reported that CDK5 plays important roles in regulating various biological and pathological processes, including cancer progression. Concerning prostate cancer, the androgen receptor (AR) is majorly involved in tumorigenesis, while CDK5 can phosphorylate AR and promotes the proliferation of prostate cancer cells. Clinical evidence has also shown that the level of CDK5 is associated with the progression of prostate cancer. Interestingly, inhibition of CDK5 prevents prostate cancer cell growth, while drug-triggered CDK5 hyperactivation leads to apoptosis. The blocking of CDK5 activity by its small interfering RNAs (siRNA) or Roscovitine, a pan-CDK inhibitor, reduces the cellular AR protein level and triggers the death of prostate cancer cells. Thus, CDK5 plays a crucial role in the growth of prostate cancer cells, and AR regulation is one of the important pathways. In this review paper, we summarize the significant studies on CDK5-mediated regulation of prostate cancer cells. We propose that the CDK5-p35 complex might be an outstanding candidate as a diagnostic marker and potential target for prostate cancer treatment in the near future.
周期蛋白依赖性激酶 5（CDK5）是细胞周期蛋白依赖性激酶家族中的一个独特成员。CDK5 通过与其调节蛋白（主要是 p35）结合而被激活，其激活在中枢神经系统（CNS）的发育和神经退行性变中至关重要。最近有报道称，CDK5 在调节包括癌症进展在内的各种生物学和病理过程中发挥重要作用。就前列腺癌而言，雄激素受体（AR）主要参与肿瘤的发生，而 CDK5 可以磷酸化 AR 并促进前列腺癌细胞的增殖。临床证据还表明，CDK5 的水平与前列腺癌的进展有关。有趣的是，抑制 CDK5 可阻止前列腺癌细胞的生长，而药物引发的 CDK5 过度激活则导致细胞凋亡。通过其小干扰 RNA（siRNA）或泛细胞周期蛋白激酶抑制剂 Roscovitine 阻断 CDK5 的活性，可降低细胞 AR 蛋白水平并引发前列腺癌细胞死亡。因此，CDK5 在前列腺癌细胞的生长中起着关键作用，AR 调节是其中一个重要途径。在这篇综述论文中，我们总结了关于 CDK5 介导的前列腺癌细胞调节的重要研究。我们提出，CDK5-p35 复合物可能是一个杰出的候选标志物和潜在的治疗靶点，用于前列腺癌的治疗。
