Future aspects of CDK5 in prostate cancer: From pathogenesis to therapeutic implications

Muhammet Oner, Eugene Lin, Mei Chih Chen, Fu Ning Hsu, G. M. Shazzad Hossain Prince, Kun Yuan Chiu, Chieh Lin Jerry Teng, Tsung Ying Yang, Hsin Yi Wang, Chia Herng Yue, Ching Han Yu, Chih Ho Lai, Jer-Tsong Hsieh, Ho Lin

Research output: Contribution to journalReview article

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number3881
JournalInternational journal of molecular sciences
Volume20
Issue number16
DOIs
Publication statusPublished - Aug 2 2019

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Keywords

  • Androgen receptor (AR)
  • Cyclin-dependent kinase 5 (CDK5)
  • P35
  • Prostate cancer

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Oner, M., Lin, E., Chen, M. C., Hsu, F. N., Shazzad Hossain Prince, G. M., Chiu, K. Y., ... Lin, H. (2019). Future aspects of CDK5 in prostate cancer: From pathogenesis to therapeutic implications. International journal of molecular sciences, 20(16), [3881]. https://doi.org/10.3390/ijms20163881