Document Type
Journal Article
Publication Title
Cancer Medicine
Volume
10
Issue
11
First Page
3689
Last Page
3699
PubMed ID
33960694
Publisher
Wiley
School
School of Medical and Health Sciences / Centre for Precision Health
RAS ID
35673
Funders
National Natural Science Foundation of China Australian-China Collaborative Grant
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.
DOI
10.1002/cam4.3916
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Chu, Q., Wang, L., Zhang, J., Wang, W., & Wang, Y. (2021). CDK5 positively regulates notch1 signaling in pancreatic cancer cells by phosphorylation. Cancer Medicine, 10(11), 3689-3699. https://doi.org/10.1002/cam4.3916