2. Academic Validation
  3. CDK5 positively regulates Notch1 signaling in pancreatic cancer cells by phosphorylation

CDK5 positively regulates Notch1 signaling in pancreatic cancer cells by phosphorylation

  • Cancer Med. 2021 Jun;10(11):3689-3699. doi: 10.1002/cam4.3916.
Qiaoyun Chu 1,  Liyong Wang 2,  Jie Zhang 3,  Wei Wang 4,  Youxin Wang 3
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
  • 2 Core Facilities for Molecular Biology, Capital Medical University, Beijing, China.
  • 3 Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China.
  • 4 Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia.
PMID: 33960694 DOI: 10.1002/cam4.3916
Abstract

The marked overexpression of cyclin-dependent kinase 5 (CDK5) or Notch1 receptor, which plays critical roles in pancreatic ductal adenocarcinoma (PDAC) development, has been detected in numerous PDAC cell lines and tissues. Although, a previous study has demonstrated that CDK5 inhibition disrupts Notch1 functions in human umbilical vein endothelial cells, the mechanism underlying Notch1 activation regulated by CDK5 remains unclear. Herein, we identified a physical interaction between CDK5 and Notch1 in PDAC cells, with the Notch1 peptide phosphorylated by CDK5/p25 kinase. CDK5 blockade resulted in the profound inhibition of Notch signaling. Accordingly, CDK5 inhibition sensitized PDAC cell proliferation and migration following Notch inhibition. In conclusion, CDK5 positively regulates Notch1 function via phosphorylation, which in turn promotes cell proliferation and migration. The combinational inhibition of CDK5 and Notch signaling may be an effective strategy in the treatment of PDAC.

Keywords

CDK5; Notch1; cell proliferation; pancreatic ductal adenocarcinoma; phosphorylation.

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