EZH2 couples pancreatic regeneration to neoplastic progression
EZH2 couples pancreatic regeneration to neoplastic progression
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DOI：
10.1101/gad.181800.111
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发表时间：
2012-03-01
影响因子：
10.5
通讯作者：
Bar-Sagi, Dafna
中科院分区：
文献类型：
--
作者：
Mallen-St Clair, Jon;Soydaner-Azeloglu, Rengin;Bar-Sagi, Dafna
虽然多梳组蛋白增强子Zeste同源物2（EZH2）因其作为细胞分化的关键调节剂的作用而被充分认识，但其在组织再生中的参与在很大程度上是未知的。在这里，我们发现EZH2在蛙皮素诱导的胰腺损伤后上调，并且通过促进祖细胞的再生增殖来进行组织修复。EZH2的缺失导致胰腺再生受损并加速KRas（G12D）驱动的瘤形成。我们的研究结果表明EZH2通过控制胰腺再生的稳态机制抑制肿瘤进展，并提供了对慢性胰腺损伤与胰腺癌风险增加之间关系的见解。
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.