FAT4 silencing promotes epithelial-to-mesenchymal transition and invasion via regulation of YAP and β-catenin activity in ovarian cancer

Shika Hanif Malgundkar, Ikram Burney, Mansour Al Moundhri, Moza Al Kalbani, Ritu Lakhtakia, Aikou Okamoto, Yahya Tamimi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Background: The adhesion molecule, FAT4, has a tumor suppressor function with a critical role in the epithelial-to-mesenchymal-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.

Original languageEnglish
Article number374
JournalBMC Cancer
Volume20
Issue number1
DOIs
Publication statusPublished - May 4 2020
Externally publishedYes

Keywords

  • FAT4
  • Invasion
  • Ovarian cancer
  • Silencing
  • YAP

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'FAT4 silencing promotes epithelial-to-mesenchymal transition and invasion via regulation of YAP and β-catenin activity in ovarian cancer'. Together they form a unique fingerprint.

Cite this