FBXW7 suppresses cell proliferation, migration, and epithelial-mesenchymal transition in endometrioid ovarian carcinoma

Epithelial ovarian carcinoma is a common gynecologic malignancy. Evidence from several studies suggests that subtypes of this cancer-specifically clear-cell ovarian carcinoma and endometrioid ovarian carcinoma (ENOC)-are associated with endometriosis. FBXW7 (F-box and WD repeat domain containing 7) is a tumor suppressor and component of an E3 ubiquitin ligase complex, which is responsible for tagging proteins for proteasomal degradation. FBXW7 is one of the most frequently dysregulated proteins of the ubiquitin-proteasome system in various human cancers. Thus, we investigated whether FBXW7 dysfunction contributes to epithelial ovarian carcinoma. We found that the level of FBXW7 was lower in endometriosis-associated ovarian carcinoma, especially ENOC. Functional assays revealed that overexpression of FBXW7 inhibited the proliferation and migration of ovarian carcinoma cells, whereas FBXW7 knockdown had the opposite effect. We also found that FBXW7 expression was associated with reduced vimentin levels, accompanied by changes in epithelial-mesenchymal transition (EMT) markers. Overexpression of FBXW7 increased E-cadherin levels while reducing N-cadherin and vimentin levels, thereby promoting the epithelial phenotype. Conversely, FBXW7 knockdown upregulated vimentin and N-cadherin levels, facilitating EMT. Co-immunoprecipitation assays indicated that FBXW7 co-precipitates with vimentin, suggesting a possible role for FBXW7 in influencing vimentin abundance. These findings highlight FBXW7 as a potential tumor suppressor in endometriosis-associated ovarian carcinoma, with effect on cell proliferation, migration, and EMT regulation. The FBXW7-vimentin association may represent previously unrecognized pathway with therapeutic relevance in ovarian carcinoma.