Repression of E-cadherin by the polycomb group protein EZH2 in cancer

Q. Cao, J. Yu, S. M. Dhanasekaran, J. H. Kim, R. S. Mani, S. A. Tomlins, R. Mehra, B. Laxman, X. Cao, J. Yu, C. G. Kleer, S. Varambally, A. M. Chinnaiyan

Research output: Contribution to journalArticle

387 Citations (Scopus)

Abstract

Enhancer of zeste homolog 2 (EZH2) is a critical component of the polycomb-repressive complex 2 (PRC2), which is involved in gene silencing and histone H3 lysine 27 methylation. EZH2 has a master regulatory function in controlling such processes as stem cell differentiation, cell proliferation, early embryogenesis and X chromosome inactivation. Although benign epithelial cells express very low levels of EZH2, increased levels of EZH2 have been observed in aggressive solid tumors such as those of the prostate, breast and bladder. The mechanism by which EZH2 mediates tumor aggressiveness is unclear. Here, we demonstrate that EZH2 mediates transcriptional silencing of the tumor suppressor gene E-cadherin by trimethylation of H3 lysine 27. Histone deacetylase inhibitors can prevent EZH2-mediated repression of E-cadherin and attenuate cell invasion, suggesting a possible mechanism that may be useful for the development of therapeutic treatments. Taken together, these observations provide a novel mechanism of E-cadherin regulation and establish a functional link between dysregulation of EZH2 and repression of E-cadherin during cancer progression.

Original languageEnglish (US)
Pages (from-to)7274-7284
Number of pages11
JournalOncogene
Volume27
Issue number58
DOIs
StatePublished - Dec 11 2008

Fingerprint

Polycomb-Group Proteins
Cadherins
Neoplasms
Lysine
Polycomb Repressive Complex 2
X Chromosome Inactivation
Histone Deacetylase Inhibitors
Enhancer of Zeste Homolog 2 Protein
Gene Silencing
Tumor Suppressor Genes
Histones
Methylation
Embryonic Development
Prostate
Cell Differentiation
Urinary Bladder
Breast
Stem Cells
Epithelial Cells
Cell Proliferation

Keywords

  • E-cadherin
  • Epigenetics
  • EZH2
  • Histone
  • Polycomb group protein

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Cao, Q., Yu, J., Dhanasekaran, S. M., Kim, J. H., Mani, R. S., Tomlins, S. A., ... Chinnaiyan, A. M. (2008). Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene, 27(58), 7274-7284. https://doi.org/10.1038/onc.2008.333

Repression of E-cadherin by the polycomb group protein EZH2 in cancer. / Cao, Q.; Yu, J.; Dhanasekaran, S. M.; Kim, J. H.; Mani, R. S.; Tomlins, S. A.; Mehra, R.; Laxman, B.; Cao, X.; Yu, J.; Kleer, C. G.; Varambally, S.; Chinnaiyan, A. M.

In: Oncogene, Vol. 27, No. 58, 11.12.2008, p. 7274-7284.

Research output: Contribution to journalArticle

Cao, Q, Yu, J, Dhanasekaran, SM, Kim, JH, Mani, RS, Tomlins, SA, Mehra, R, Laxman, B, Cao, X, Yu, J, Kleer, CG, Varambally, S & Chinnaiyan, AM 2008, 'Repression of E-cadherin by the polycomb group protein EZH2 in cancer', Oncogene, vol. 27, no. 58, pp. 7274-7284. https://doi.org/10.1038/onc.2008.333
Cao Q, Yu J, Dhanasekaran SM, Kim JH, Mani RS, Tomlins SA et al. Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene. 2008 Dec 11;27(58):7274-7284. https://doi.org/10.1038/onc.2008.333
Cao, Q. ; Yu, J. ; Dhanasekaran, S. M. ; Kim, J. H. ; Mani, R. S. ; Tomlins, S. A. ; Mehra, R. ; Laxman, B. ; Cao, X. ; Yu, J. ; Kleer, C. G. ; Varambally, S. ; Chinnaiyan, A. M. / Repression of E-cadherin by the polycomb group protein EZH2 in cancer. In: Oncogene. 2008 ; Vol. 27, No. 58. pp. 7274-7284.
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