The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program
The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program
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DOI：
10.1101/gad.1978810
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发表时间：
2010-11-01
影响因子：
10.5
通讯作者：
Pan, Duojia
中科院分区：
文献类型：
--
作者：
Cai, Jing;Zhang, Nailing;Pan, Duojia
虽然Hippo信号在器官大小控制中的发育作用得到了很好的理解，但这一途径在组织再生中如何发挥作用在很大程度上是未知的。在这里，我们解决这个问题，使用葡聚糖硫酸钠（DSS）诱导的结肠再生模型。我们发现再生隐窝表达升高的Yes相关蛋白（雅普）水平。雅普的失活在正常的内环境稳定下不会引起明显的肠缺陷，但严重损害DSS诱导的肠再生。相反，雅普的过度活化导致DSS治疗后广泛的早发性息肉形成。因此，雅普癌蛋白必须在组织再生中被精确地控制，以允许补偿性增殖并防止组织再生程序的内在致癌潜力。
Although a developmental role for Hippo signaling in organ size control is well appreciated, how this pathway functions in tissue regeneration is largely unknown. Here we address this issue using a dextran sodium sulfate (DSS)-induced colonic regeneration model. We find that regenerating crypts express elevated Yes-associated protein (YAP) levels. Inactivation of YAP causes no obvious intestinal defects under normal homeostasis, but severely impairs DSS-induced intestinal regeneration. Conversely, hyperactivation of YAP results in widespread early-onset polyp formation following DSS treatment. Thus, the YAP oncoprotein must be exquisitely controlled in tissue regeneration to allow compensatory proliferation and prevent the intrinsic oncogenic potential of a tissue regeneration program.