CDK5 positively regulates Notch1 signaling in pancreatic cancer cells by phosphorylation
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 di...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-06-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.3916 |
| _version_ | 1830081778887426048 |
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| author | Qiaoyun Chu Liyong Wang Jie Zhang Wei Wang Youxin Wang |
| author_facet | Qiaoyun Chu Liyong Wang Jie Zhang Wei Wang Youxin Wang |
| author_sort | Qiaoyun Chu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T15:46:56Z |
| format | Article |
| id | doaj.art-da2107d15ed9483183fd336aaab0ccdc |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-14T15:46:56Z |
| publishDate | 2021-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-da2107d15ed9483183fd336aaab0ccdc2022-12-21T22:55:28ZengWileyCancer Medicine2045-76342021-06-0110113689369910.1002/cam4.3916CDK5 positively regulates Notch1 signaling in pancreatic cancer cells by phosphorylationQiaoyun Chu0Liyong Wang1Jie Zhang2Wei Wang3Youxin Wang4Department of Biochemistry and Molecular Biology School of Basic Medical SciencesCapital Medical University Beijing ChinaCore Facilities for Molecular Biology Capital Medical University Beijing ChinaBeijing Key Laboratory of Clinical Epidemiology School of Public HealthCapital Medical University Beijing ChinaCentre for Precision Health School of Medical and Health Sciences Edith Cowan University Perth AustraliaBeijing Key Laboratory of Clinical Epidemiology School of Public HealthCapital Medical University Beijing ChinaAbstract 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.https://doi.org/10.1002/cam4.3916CDK5cell proliferationNotch1pancreatic ductal adenocarcinomaphosphorylation |
| spellingShingle | Qiaoyun Chu Liyong Wang Jie Zhang Wei Wang Youxin Wang CDK5 positively regulates Notch1 signaling in pancreatic cancer cells by phosphorylation Cancer Medicine CDK5 cell proliferation Notch1 pancreatic ductal adenocarcinoma phosphorylation |
| title | CDK5 positively regulates Notch1 signaling in pancreatic cancer cells by phosphorylation |
| title_full | CDK5 positively regulates Notch1 signaling in pancreatic cancer cells by phosphorylation |
| title_fullStr | CDK5 positively regulates Notch1 signaling in pancreatic cancer cells by phosphorylation |
| title_full_unstemmed | CDK5 positively regulates Notch1 signaling in pancreatic cancer cells by phosphorylation |
| title_short | CDK5 positively regulates Notch1 signaling in pancreatic cancer cells by phosphorylation |
| title_sort | cdk5 positively regulates notch1 signaling in pancreatic cancer cells by phosphorylation |
| topic | CDK5 cell proliferation Notch1 pancreatic ductal adenocarcinoma phosphorylation |
| url | https://doi.org/10.1002/cam4.3916 |
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