FBXW2 inhibits the progression of gastric cancer via promoting ?-catenin ubiquitylation.
Background: F-box and WD-repeat-containing protein 2 (FBXW2), an E3 ubiquitin ligase, may play a crucial role in tumorigenesis. However, its function in gastric cancer remains unknown. Methods: The expression levels of FBXW2 and ?-catenin in gastric cancer samples were analyzed using RT-PCR and immunohistochemistry, with Pearson correlation analysis to assess ... their relationship. AGS and HGC-27 gastric cancer cells were transfected with sh-FBXW2, and their viability was evaluated using the CCK8 assay, while invasion ability was assessed via the transwell assay. Western blotting was performed to measure the expression levels of FBXW2, ?-catenin, GSK3?, and Axin2 in AGS cells. Additionally, a ubiquitination assay was conducted to examine the effect of sh-FBXW2 on ?-catenin ubiquitination. Immunoprecipitation was used to determine the potential interaction between FBXW2 and ?-catenin. Results: FBXW2 expression was downregulated, whereas ?-catenin expression was upregulated in gastric cancer tissues compared to adjacent normal tissues, showing a significant negative correlation (r = -0.52, P < 0.001). Knockdown of FBXW2 (sh-FBXW2) promoted gastric cancer cell viability and invasion while increasing ?-catenin expression and reducing GSK3? and Axin2 levels. Furthermore, FBXW2 was found to bind ?-catenin and facilitate its ubiquitination, leading to enhanced nuclear translocation of ?-catenin. Conclusions: FBXW2 suppresses gastric cancer progression by promoting ?-catenin ubiquitination, highlighting its potential as a therapeutic target.
Mesh Terms:
Axin Protein, Carcinogenesis, Cell Line, Tumor, Cell Movement, Cell Proliferation, Disease Progression, F-Box Proteins, Female, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Glycogen Synthase Kinase 3 beta, Humans, Male, Middle Aged, Neoplasm Invasiveness, Stomach Neoplasms, Ubiquitination, beta Catenin
Axin Protein, Carcinogenesis, Cell Line, Tumor, Cell Movement, Cell Proliferation, Disease Progression, F-Box Proteins, Female, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Glycogen Synthase Kinase 3 beta, Humans, Male, Middle Aged, Neoplasm Invasiveness, Stomach Neoplasms, Ubiquitination, beta Catenin
Int J Med Sci
Date: Apr. 14, 2025
PubMed ID: 40225854
View in: Pubmed Google Scholar
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