Background: The adhesion molecule, FAT4, has a tumor suppressor function with a critical role in the epithelial-tomesenchymal-transition (EMT) and anti-malignant growth in several cancers. No study has investigated yet its role in epithelial ovarian cancer (EOC) progression. In the present study, we examined the role of FAT4 in proliferation and metastasis, and its mechanisms of interaction in these processes. Methods: We have performed cell viability, colony formation, and invasion assays in ovarian cancer cells treated with siRNA to knockdown FAT4 gene expression. The regulatory effects of FAT4 on proteins involved in apoptotic, Wnt, Hippo, and retinoblastoma signaling pathways were evaluated by Western blotting following FAT4 repression. Also, 426 ovarian tumor samples and 88 non-tumor samples from the Gene Expression Profiling Interactive Analysis (GEPIA) database were analyzed for the expression of FAT4. Pearson's correlation was performed to determine the correlation between FAT4 and the E2F5, cyclin D1, cdk4, and caspase 9 expressions. Results: Lower expression of FAT4 was observed in ovarian cancer cell lines and human samples as compared to non-malignant tissues. This down-regulation seems to enhance cell viability, invasion, and colony formation. Silencing FAT4 resulted in the upregulation of E2F5, vimentin, YAP, β-catenin, cyclin D1, cdk4, and Bcl2, and in the downregulation of GSK-3-β, and caspase 9 when compared to control. Furthermore, regulatory effects of FAT4 on the EMT and aggressive phenotype seem to occur through Hippo, Wnt, and cell cycle pathways. Conclusion: FAT4 downregulation promotes increased growth and invasion through the activation of Hippo and Wnt-β-catenin pathways.

Background: E2F5 is a transcription factor that is overexpressed in the early stages of ovarian cancer and has been suggested as a potential biomarker for early detection. In this study, we aimed to examine the role of E2F5 in invasion and proliferation of ovarian cancer cells. Materials and Methods: We performed cell viability, colony formation, and invasion assays using ovarian cancer cells treated with siRNA to knock down the E2F5 gene. The regulatory effects of E2F5 on proteins involved in the apoptotic, Wnt, Hippo, and retinoblastoma signaling pathways were evaluated by western blotting following E2F5 repression. In addition, we analyzed data available on Gene Expression Profiling Interactive Analysis for correlations between E2F5 and YAP, b-catenin, cyclin D1, cdk4, and caspase-9. Results: E2F5 was highly expressed in ovarian cancer cell lines and samples when compared to the nonmalignant tissues. Downregulation of E2F5 inhibited cell viability and invasion and promoted the phosphorylation of YAP, GSK-3-b, b-catenin, and retinoblastoma. However, cyclin D1, cdk4, and caspase-9 were downregulated when compared to control. Conclusion: Overall, E2F5 promotes ovarian carcinogenesis via the regulation of Hippo and Wnt pathways.

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More than two-thirds of epithelial ovarian cancer (EOC) patients are diagnosed at advanced stages due to the lack of sensitive biomarkers. Currently, exosomes are intensively investigated as non-invasive cancer diagnostic markers. Exosomes are nanovesicles released in the extracellular milieu with the potential to modulate recipient cells' behavior. EOC cells release many altered exosomal cargoes that exhibit clinical relevance to tumor progression. Exosomes represent powerful therapeutic tools (drug carriers or vaccines), posing a promising option in clinical practice for curing EOC in the near future. In this review, we highlight the importance of exosomes in cell–cell communication, epithelial–mesenchymal transition (EMT), and their potential to serve as diagnostic and prognostic factors, particularly in EOC.