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Updated: Apr 27, 2026

Isolation, Culture, and Characterization of Prostate Cancer-Associated Fibroblasts
Published on: August 1, 2025
Post-translational regulation of COX2 activity by FYN in prostate cancer cells
Anna Alexanian1, Bradley Miller1, Marla Chesnik2
1Division of Nephrology and Kidney Disease Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Abstract:
While increased COX2 expression and prostaglandin levels are elevated in human cancers, the mechanisms of COX2 regulation at the post-translational level are unknown. Initial observation that COX2 forms adduct with non-receptor tyrosine kinase FYN, prompted us to study FYN-mediated post-translational regulation of COX2. We found that FYN increased COX2 activity in prostate cancer cells DU145, independent of changes in COX2 or COX1 protein expression levels. We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity.
Insights
FYN kinase phosphorylates COX2 at Tyr 446, increasing its activity in prostate cancer cells. This FYN-mediated phosphorylation enhances cyclooxygenase-2 (COX2) activity, independent of protein levels.
Area of Science:
- Molecular Biology
- Cancer Research
- Biochemistry
Background:
- Elevated cyclooxygenase-2 (COX2) expression and prostaglandin levels are hallmarks of human cancers.
- Mechanisms regulating COX2 at the post-translational level remain largely unknown.
- Cyclooxygenase-2 (COX2) has been observed to form adducts with the non-receptor tyrosine kinase FYN.
Purpose of the Study:
- To investigate the role of FYN-mediated post-translational regulation of COX2.
- To determine if FYN affects COX2 activity in prostate cancer cells.
Main Methods:
- Utilized DU145 prostate cancer cells to study FYN-mediated COX2 regulation.
- Assessed COX2 activity in response to FYN interaction.
- Investigated FYN-mediated phosphorylation of human COX2 at Tyr 446 using phospho-mimetic and phosphorylation-blocking mutations.
Main Results:
- FYN significantly increased COX2 activity in DU145 prostate cancer cells.
- This increase in COX2 activity was independent of changes in COX2 or COX1 protein expression levels.
- FYN was found to phosphorylate human COX2 on Tyr 446.
Conclusions:
- FYN-mediated phosphorylation of COX2 at Tyr 446 is a key mechanism for increasing COX2 activity.
- Phosphorylation of COX2 by FYN enhances its enzymatic activity, potentially contributing to cancer progression.
- Targeting the FYN-COX2 interaction may offer novel therapeutic strategies in cancers with elevated COX2.
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