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

Research output: Contribution to journalArticle

7 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
Externally publishedYes

Fingerprint

Epithelial-Mesenchymal Transition
Squamous Cell Carcinoma
DNA
Neoplasms
Oral Stage
Cell Line
Wnt Signaling Pathway
Gene Silencing
DNA Methylation
Cadherins
Methylation
Genes

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Kurasawa, Y., Kozaki, K., Pimkhaokham, A., Muramatsu, T., Ono, H., Ishihara, 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

Stabilization of phenotypic plasticity through mesenchymal-specific DNA hypermethylation in cancer cells. / Kurasawa, Y.; Kozaki, K.; Pimkhaokham, A.; Muramatsu, T.; Ono, H.; Ishihara, T.; Uzawa, N.; Imoto, I.; Amagasa, T.; Inazawa, J.

In: Oncogene, Vol. 31, No. 15, 12.04.2012, p. 1963-1974.

Research output: Contribution to journalArticle

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, vol. 31, no. 15, pp. 1963-1974. https://doi.org/10.1038/onc.2011.373
Kurasawa Y, Kozaki K, Pimkhaokham A, Muramatsu T, Ono H, Ishihara T et al. Stabilization of phenotypic plasticity through mesenchymal-specific DNA hypermethylation in cancer cells. Oncogene. 2012 Apr 12;31(15):1963-1974. https://doi.org/10.1038/onc.2011.373
Kurasawa, Y. ; Kozaki, K. ; Pimkhaokham, A. ; Muramatsu, T. ; Ono, H. ; Ishihara, T. ; Uzawa, N. ; Imoto, I. ; Amagasa, T. ; Inazawa, J. / Stabilization of phenotypic plasticity through mesenchymal-specific DNA hypermethylation in cancer cells. In: Oncogene. 2012 ; Vol. 31, No. 15. pp. 1963-1974.
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