Stabilization of phenotypic plasticity through mesenchymal-specific DNA hypermethylation in cancer cells

Y. Kurasawa, K. Kozaki, A. Pimkhaokham, T. Muramatsu, H. Ono, T. Ishihara, N. Uzawa, I. Imoto, T. Amagasa, J. Inazawa

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8 Citations (Scopus)

Abstract

The epithelial-mesenchymal transition (EMT) has a crucial role in normal and disease processes including tumor progression. In this study, we first classified epithelial-like and mesenchymal-like oral squamous cell carcinoma (OSCC) cell lines based on expression profiles of typical EMT-related genes using a panel of 18 OSCC cell lines. Then, we performed methylation-based and expression-based analyses of components of the Wnt signaling pathway, and identified WNT7A and WNT10A as genes silenced by mesenchymal-specific DNA hypermethylation in OSCCs. A significant association was revealed between some clinicopathological findings and the DNA methylation status of WNT7A (normal vs tumor, P=0.007; T1-2 vs T3-4, P=0.040; I-III vs IV, P=0.016) and WNT10A (N0-N1 vs N2-N3, P=0.046) in the advanced stages of OSCC. Moreover, we found that E-cadherin expression in cancer cells may be positively regulated by WNT7A, whose expression is negatively regulated by mesenchymal-specific DNA hypermethylation or ZEB1 in mesenchymal-like OSCC cells. Our findings indicate that epithelial-specific gene silencing through mesenchymal-specific DNA hypermethylation may stabilize the phenotypic plasticity of cancer cells during EMT/MET.

Original languageEnglish
Pages (from-to)1963-1974
Number of pages12
JournalOncogene
Volume31
Issue number15
DOIs
Publication statusPublished - Apr 12 2012

Keywords

  • DNA hypermethylation
  • EMT
  • WNT10A
  • WNT7A
  • oral squamous cell carcinoma

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Kurasawa, Y., Kozaki, K., Pimkhaokham, A., Muramatsu, T., Ono, H., Ishihara, T., Uzawa, N., Imoto, I., Amagasa, T., & Inazawa, J. (2012). Stabilization of phenotypic plasticity through mesenchymal-specific DNA hypermethylation in cancer cells. Oncogene, 31(15), 1963-1974. https://doi.org/10.1038/onc.2011.373