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Updated: Mar 31, 2026

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对Lgr5 ((+) 干细胞的依赖于Yap的重编程驱动肠道再生和癌症
Alex Gregorieff1, Yu Liu1,2, Mohammad R Inanlou1
1Centre for Systems Biology, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
Nature
|October 28, 2015
概括
在受伤后,Hippo途径效应器Yap重新编程肠道干细胞 (ISC),抑制Wnt信号以促进细胞再生和存活. 在结肠癌的开始和进展中也起着至关重要的作用.
科学领域:
- 细胞生物学
- 发育生物学
- 癌症生物学
背景情况:
- 在正常情况下,肠道上皮层不断更新,由Lgr5(+) 肠道干细胞 (ISC) 和Wnt信号驱动.
- 在受伤后ISC再生的机制尚未完全理解.
- 河马信号通路调节组织生长, 对于再生至关重要.
研究的目的:
- 在受伤后的肠道干细胞再生中,
- 阐明Yap影响ISC重编程和再生的分子机制.
- 确定Yap在结肠癌发病和进展中的作用.
主要方法:
- 在暴露于电离辐射的小鼠中进行的研究.
- 对Yap缺乏器官的分析及其对EGFR连接物epiregulin的反应.
- 研究雅普在结肠癌小鼠模型中的作用.
- 早期APC突变致瘤细胞的体内研究.
主要成果:
- 在辐射损伤后肠上皮的恢复至关重要.
- 通过抑制Wnt信号和促进Egf通路激活,Yap暂时重新编程Lgr5(+) ISC.
- 在Apc(Min) 鼠标模型中,Yap无活化消除了腺瘤,并且对于瘤发起细胞的进展是必要的.
- 它抑制了Paneth细胞的分化,并诱导了包括Egfr信号在内的再生程序.
结论:
- 在组织损伤时,Yap会通过抑制Wnt的恒常程序,并通过EGFR信号诱导再生程序来重新编程Lgr5(+) ISC.
- 雅普再生途径是结肠癌开始和进展的关键驱动因素.
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