EZH2 couples pancreatic regeneration to neoplastic progression

  1. Dafna Bar-Sagi1,9
  1. 1Department of Biochemistry, New York University School of Medicine, New York, New York 10016, USA;
  2. 2New York University School of Medicine, New York, New York 10016, USA;
  3. 3Department of Surgery, New York University School of Medicine, New York, New York 10016, USA;
  4. 4Howard Hughes Medical Institute, New York, New York 10016, USA
    1. 5 These authors contributed equally to this work.

    • Present addresses: 6Department of Surgery, Division of Head and Neck Surgery, University of California at Los Angeles, Los Angeles, CA 90095, USA;

    • 7 Abramson Family Cancer Research Institute, Howard Hughes Medical Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;

    • 8 Institut Curie, 75005 Paris, France.

    Abstract

    Although the polycomb group protein Enhancer of Zeste Homolog 2 (EZH2) is well recognized for its role as a key regulator of cell differentiation, its involvement in tissue regeneration is largely unknown. Here we show that EZH2 is up-regulated following cerulein-induced pancreatic injury and is required for tissue repair by promoting the regenerative proliferation of progenitor cells. Loss of EZH2 results in impaired pancreatic regeneration and accelerates KRasG12D-driven neoplasia. Our findings implicate EZH2 in constraining neoplastic progression through homeostatic mechanisms that control pancreatic regeneration and provide insights into the documented link between chronic pancreatic injury and an increased risk for pancreatic cancer.

    Keywords

    Footnotes

    • Received October 24, 2011.
    • Accepted February 2, 2012.
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