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Maintaining cell identity: PRC2-mediated regulation of transcription and cancer

Itys Comet1, Eva M Riising2, Benjamin Leblanc1,3

  • 1Biotech Research and Innovation Centre (BRIC) and the Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.

Nature Reviews. Cancer
|September 24, 2016
PubMed

Insights

Enhancer of zeste homologue 2 (EZH2), a key protein in cancer, plays dual roles in tumor suppression and promotion. Its function in maintaining gene repression explains these opposing effects in cancer development.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Research

Background:

  • Enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2).
  • EZH2 is implicated in the development and progression of numerous cancers.
  • Specific EZH2 inhibitors are currently in clinical trials for cancer treatment.

Purpose of the Study:

  • To reconcile the apparently opposing roles of PRC2 in cancer.
  • To elucidate the molecular mechanism underlying EZH2's dual function in oncogenesis and tumor suppression.

Main Methods:

  • The study proposes a hypothesis based on existing observations and molecular function.
  • Analysis of the transcriptional repression state of PRC2 target genes.

Main Results:

  • PRC2 exhibits both oncogenic and tumor-suppressive functions in different cancer contexts.
  • These dual roles are attributed to PRC2's function in maintaining, not initiating, transcriptional repression.

Conclusions:

  • The context-dependent roles of PRC2 in cancer are explained by its function as a maintenance factor for transcriptional repression.
  • Understanding this mechanism is crucial for developing effective EZH2-targeted cancer therapies.

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