Oncogenic roles of enhancer of zeste homolog 1/2 in hematological malignancies

Cancer Sci. 2018 Aug;109(8):2342-2348. doi: 10.1111/cas.13655. Epub 2018 Jun 27.

Abstract

Polycomb group (PcG) proteins regulate the expression of target genes by modulating histone modifications and are representative epigenetic regulators that maintain the stemness of embryonic and hematopoietic stem cells. Histone methyltransferases enhancer of zeste homolog 1 and 2 (EZH1/2), which are subunits of polycomb repressive complexes (PRC), are recurrently mutated or highly expressed in many hematological malignancies. EZH2 has a dual function in tumorigenesis as an oncogene and tumor suppressor gene, and targeting PRC2, in particular EZH1/2, for anticancer therapy has been extensively developed in the clinical setting. Here, we review the oncogenic function of EZH1/2 and introduce new therapeutic drugs targeting these enzymes.

Keywords: enhancer of zeste homolog 1 and 2; epigenetics; histone methyltransferase; polycomb repressive complexes; transcriptional repression.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Enhancer of Zeste Homolog 2 Protein / genetics*
  • Hematologic Neoplasms / genetics*
  • Humans
  • Oncogenes / genetics*
  • Polycomb Repressive Complex 2 / genetics*
  • Polycomb-Group Proteins / genetics

Substances

  • Polycomb-Group Proteins
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2