EZH2 couples pancreatic regeneration to neoplastic progression

被引：102

作者：

Mallen-St Clair, Jon ^{[1
]}

Soydaner-Azeloglu, Rengin ^{[1
]}

Lee, Kyoung Eun ^{[1
]}

Taylor, Laura ^{[1
]}

Livanos, Alexandra

Pylayeva-Gupta, Yuliya ^{[1
]}

Miller, George ^{[2
]}

Margueron, Raphael ^{[1
]}

Reinberg, Danny ^{[1
,3
]}

Bar-Sagi, Dafna ^{[1
]}

机构：

[1] NYU, Sch Med, Dept Biochem, New York, NY 10016 USA

[2] NYU, Sch Med, Dept Surg, New York, NY 10016 USA

[3] Howard Hughes Med Inst, New York, NY 10016 USA

来源：

GENES & DEVELOPMENT | 2012年 / 26卷 / 05期

关键词：

EZH2; pancreas; regeneration; cancer; TUMOR-CELL PROLIFERATION; ACINAR-CELL; BETA-CELL; EXPRESSION; CANCER; INFLAMMATION; METHYLATION; ENHANCER; HEDGEHOG; GENE;

D O I：

10.1101/gad.181800.111

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 KRas(G12D)-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.

引用

页码：439 / 444

页数：6

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