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

Int J Mol Sci. 2020 Mar 7;21(5):1848. doi: 10.3390/ijms21051848.


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.

Keywords: DNA methylation; LY75; Wnt/β-catenin; epithelial ovarian cancer; epithelial–mesenchymal transition; reduced representation bisulfite sequencing.

MeSH terms

  • Antigens, CD / genetics*
  • Carcinoma, Ovarian Epithelial / pathology*
  • Cell Line, Tumor
  • DNA Methylation / genetics*
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lectins, C-Type / genetics*
  • Minor Histocompatibility Antigens / genetics*
  • Ovarian Neoplasms / pathology*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Receptors, Cell Surface / genetics*
  • Wnt Signaling Pathway / genetics*
  • beta Catenin / antagonists & inhibitors*


  • Antigens, CD
  • CTNNB1 protein, human
  • DEC-205 receptor
  • Lectins, C-Type
  • Minor Histocompatibility Antigens
  • RNA, Small Interfering
  • Receptors, Cell Surface
  • beta Catenin