EZH2 couples pancreatic regeneration to neoplastic progression
- Jon Mallen-St. Clair1,5,6,
- Rengin Soydaner-Azeloglu1,5,
- Kyoung Eun Lee1,7,
- Laura Taylor1,
- Alexandra Livanos2,
- Yuliya Pylayeva-Gupta1,
- George Miller3,
- Raphaël Margueron1,8,
- Danny Reinberg1,4 and
- Dafna Bar-Sagi1,9
- 1Department of Biochemistry, New York University School of Medicine, New York, New York 10016, USA;
- 2New York University School of Medicine, New York, New York 10016, USA;
- 3Department of Surgery, New York University School of Medicine, New York, New York 10016, USA;
- 4Howard Hughes Medical Institute, New York, New York 10016, USA
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↵5 These authors contributed equally to this work.
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.
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Footnotes
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↵9 Corresponding author.
E-mail dafna.bar-sagi{at}nyumc.org.
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.181800.111.
- Received October 24, 2011.
- Accepted February 2, 2012.
- Copyright © 2012 by Cold Spring Harbor Laboratory Press