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

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.

• Authors: Y Kurasawa, K Kozaki, A Pimkhaokham, T Muramatsu, H Ono, T Ishihara, N Uzawa, I Imoto, T Amagasa, J Inazawa
• Journal: Oncogene (Oncogene) Vol. 31 Issue 15 Pg. 1963-74 (Apr 12 2012) ISSN: 1476-5594 [Electronic] England
• PMID: 21874048 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• WNT10A protein, human
• WNT7A protein, human
• Wnt Proteins

Topics

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Squamous Cell (genetics)
• Cell Line, Tumor
• DNA Methylation
• Epithelial-Mesenchymal Transition
• Female
• Gene Silencing
• Humans
• Male
• Middle Aged
• Mouth Neoplasms (genetics)
• Phenotype
• Wnt Proteins (genetics)
• Wnt Signaling Pathway