Enhancer of zeste homolog 2 downregulates E‐cadherin by mediating histone H3 methylation in gastric cancer cells
Open Access
- 28 March 2008
- journal article
- Published by Wiley in Cancer Science
- Vol. 99 (4), 738-746
- https://doi.org/10.1111/j.1349-7006.2008.00743.x
Abstract
Overexpression of enhancer of zeste homolog 2 (EZH2), an epigenetic repressor, occurs in various malignancies and is associated with poor prognosis; however, the functional role of EZH2 overexpression in cancer versus non-cancerous tissue remains unclear. In this study, we found an inverse correlation between EZH2 and E-cadherin gene expression in gastric cancer cells. Knockdown of EZH2 by short interfering RNA in gastric cancer cells resulted in a restoration of the E-cadherin gene. We showed that the EZH2 complex existed with histone H3 and Lys27, which were methylated on E-cadherin promoter regions in gastric cancer cells. The restoration of E-cadherin was not involved in the change of the DNA methylation status in the E-cadherin promoter region. Immunofluorescence staining confirmed the expression of E-cadherin protein present in the cell membrane was restored after knockdown of EZH2, resulting in changing the cancer phenotype, such as its invasive capacity. In vivo, the relationship of inverse expression between EZH2 protein and E-cadherin protein was observed at the individual cellular level in gastric cancer tissue. This study provides into the mechanisms underlying the functional role of EZH2 overexpression in gastric cancer cells and a new modality of regulation of E-cadherin expression in silencing mechanisms of tumor suppressor genes. Our present study paves the way for exploring the blockade of EZH2 overexpression as a novel approach to treating cancer. (Cancer Sci 2008; 99: 738–746)Keywords
This publication has 44 references indexed in Scilit:
- SUZ12 Is Required for Both the Histone Methyltransferase Activity and the Silencing Function of the EED-EZH2 ComplexMolecular Cell, 2004
- The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3Current Opinion in Genetics & Development, 2004
- Focus on gastric cancerCancer Cell, 2004
- Suv39h-Mediated Histone H3 Lysine 9 Methylation Directs DNA Methylation to Major Satellite Repeats at Pericentric HeterochromatinCurrent Biology, 2003
- Role of Histone Methyltransferase G9a in CpG Methylation of the Prader-Willi Syndrome Imprinting CenterPublished by Elsevier BV ,2003
- Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste proteinGenes & Development, 2002
- Role of Histone H3 Lysine 27 Methylation in Polycomb-Group SilencingScience, 2002
- Histone Methyltransferase Activity of a Drosophila Polycomb Group Repressor ComplexCell, 2002
- Drosophila Enhancer of Zeste/ESC Complexes Have a Histone H3 Methyltransferase Activity that Marks Chromosomal Polycomb SitesCell, 2002
- Inactivation of the E-Cadherin-Mediated Cell Adhesion System in Human CancersThe American Journal of Pathology, 1998