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Proteomic Changes Associated With Endogenous FBXW7 Mutations in Moderately Differentiated Endometrial Cancer Cells
Mary Ellen Urick1, Suresh Kumar Chalapareddy1, Eun-Jeong Yu1
1Reproductive Cancer Genetics Section, Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Cancer Medicine
|March 15, 2025
Summary
Endometrial cancer (EC) is linked to FBXW7 gene mutations. This study reveals proteomic changes, including elevated galectin-3 and TROP2 levels, offering potential therapeutic targets for EC.
Area of Science:
- Oncology
- Proteomics
- Cancer Genomics
Background:
- Endometrial cancer (EC) is a significant health concern for women in the US.
- The FBXW7 tumor suppressor gene is frequently altered in EC.
- FBXW7 mutations impact protein degradation pathways.
Purpose of the Study:
- To investigate the proteomic and phosphoproteomic alterations in EC cells with endogenous FBXW7 mutations.
- To identify key proteins affected by FBXW7 loss-of-function.
Main Methods:
- Quantitative LC-MS/MS was employed to analyze proteomes and phosphoproteomes.
- Two FBXW7-mutated EC cell lines were compared to isogenic controls.
- Western blotting validated key protein expression changes.
Main Results:
- 397 proteins and/or phosphoproteins showed significant differential expression.
- Elevated levels of TROP2, galectin-3, ASS1, and PLCG2 were observed in mutated cells.
- These findings were confirmed through orthogonal validation.
Conclusions:
- FBXW7 mutations in EC lead to distinct proteomic and phosphoproteomic profiles.
- Increased galectin-3 and TROP2 present potential therapeutic targets for EC treatment.
- This research provides insights into the molecular consequences of FBXW7 alterations in EC.
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