SET8 promotes epithelial-mesenchymal transition and confers TWIST dual transcriptional activities

Fen Yang, Luyang Sun, Qian Li, Xiao Han, Liandi Lei, Hua Zhang, Yongfeng Shang

Research output: Contribution to journalArticle

138 Scopus citations

Abstract

SET8 is implicated in transcriptional regulation, heterochromatin formation, genomic stability, cell-cycle progression, and development. As such, it is predicted that SET8 might be involved in the development and progression of tumour. However, whether and how SET8 might be implicated in tumourigenesis is currently unknown. Here, we report that SET8 is physically associated with TWIST, a master regulator of epithelial-mesenchymal transition (EMT). We demonstrated that SET8 and TWIST are functionally interdependent in promoting EMT and enhancing the invasive potential of breast cancer cells in vitro and in vivo. We showed that SET8 acts as a dual epigenetic modifier on the promoters of the TWIST target genes E-cadherin and N-cadherin via its H4K20 monomethylation activity. Significantly, in breast carcinoma samples, SET8 expression is positively correlated with metastasis and the expression of TWIST and N-cadherin and negatively correlated with E-cadherin. Together, our experiments revealed a novel role for SET8 in tumour invasion and metastasis and provide a molecular mechanism underlying TWIST-promoted EMT, suggesting SET8 as a potential target for intervention of the metastasis of breast cancer.

Original languageEnglish (US)
Pages (from-to)110-123
Number of pages14
JournalEMBO Journal
Volume31
Issue number1
DOIs
Publication statusPublished - Jan 4 2012

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Keywords

  • breast cancer
  • EMT
  • metastasis
  • SET8
  • TWIST

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

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