LY75 Ablation Mediates Mesenchymal-Epithelial Transition (MET) in Epithelial Ovarian Cancer (EOC) Cells Associated with DNA Methylation Alterations and Suppression of the Wnt/β-Catenin Pathway.
Sadia MehdiMagdalena BachvarovaMarie-Pier Scott-BoyerArnaud DroitDimcho BachvarovPublished in: International journal of molecular sciences (2020)
Growing evidence demonstrates that epithelial-mesenchymal transition (EMT) plays an important role in epithelial ovarian cancer (EOC) progression and spreading; however, its molecular mechanisms remain poorly defined. We have previously shown that the antigen receptor LY75 can modulate EOC cell phenotype and metastatic potential, as LY75 depletion directed mesenchymal-epithelial transition (MET) in EOC cell lines with mesenchymal phenotype. We used the LY75-mediated modulation of EMT as a model to investigate for DNA methylation changes during EMT in EOC cells, by applying the reduced representation bisulfite sequencing (RRBS) methodology. Numerous genes have displayed EMT-related DNA methylation patterns alterations in their promoter/exon regions. Ten selected genes, whose DNA methylation alterations were further confirmed by alternative methods, were further identified, some of which could represent new EOC biomarkers/therapeutic targets. Moreover, our methylation data were strongly indicative for the predominant implication of the Wnt/β-catenin pathway in the EMT-induced DNA methylation variations in EOC cells. Consecutive experiments, including alterations in the Wnt/β-catenin pathway activity in EOC cells with a specific inhibitor and the identification of LY75-interacting partners by a proteomic approach, were strongly indicative for the direct implication of the LY75 receptor in modulating the Wnt/β-catenin signaling in EOC cells.
Keyphrases
- dna methylation
- epithelial mesenchymal transition
- induced apoptosis
- genome wide
- stem cells
- cell cycle arrest
- gene expression
- cell proliferation
- bone marrow
- cell death
- squamous cell carcinoma
- oxidative stress
- single cell
- tyrosine kinase
- transforming growth factor
- risk assessment
- cell therapy
- endothelial cells
- big data
- diabetic rats
- binding protein
- hiv infected
- bioinformatics analysis