Hippo信号通路在肠道稳态、再生及癌变过程中的作用及机制

doi:10.16288/j.yczz.17-048

遗传 ›› 2017, Vol. 39 ›› Issue (7): 588-596.doi: 10.16288/j.yczz.17-048

Hippo信号通路在肠道稳态、再生及癌变过程中的作用及机制

顾远¹(),张雷²,余发星¹()

1. 复旦大学附属儿科医院暨生物医学研究院,上海 200032
2. 中国科学院上海生命科学研究院生物化学与细胞生物学研究所,上海 200031

收稿日期:2017-02-17 修回日期:2017-04-10 出版日期:2017-07-20 发布日期:2017-05-23
作者简介:顾远,临床医学八年制,专业方向：临床医学。E-mail: yuangu14@fudan.edu.cn|余发星,研究员,博士生导师,研究方向：细胞生物学。E-mail: fxyu@fudan.edu.cn
基金资助:
国家自然科学基金面上项目(81622038,31571479)

Functions and regulations of the Hippo signaling pathway in intestinal homeostasis, regeneration and tumorigenesis

Yuan Gu¹(),Lei Zhang²,Faxing Yu¹(),

1. Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
2. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

Received:2017-02-17 Revised:2017-04-10 Online:2017-07-20 Published:2017-05-23
Supported by:
the National Natural Science Foundation of China(81622038,31571479)

摘要/Abstract

摘要：

肠道是人体最重要的消化器官之一,急慢性肠炎、肠道肿瘤等肠道疾病严重威胁着人类的健康,因此对肠道生理及病理机制的研究具有重要的科学意义及临床价值。Hippo信号通路在细胞增殖与分化、组织损伤再生、肿瘤发生和发展过程中起重要作用,参与肠道中众多生理及病理进程的调控。本文结合近年来肠道相关Hippo信号通路的研究进展,对该领域的前沿信息进行概括总结,重点阐述了Hippo信号在肠稳态、再生与癌变过程中的作用,并在此基础上展望了肠道中Hippo信号通路研究的前景及潜在的临床价值。

关键词: 肠道, Hippo信号通路, YAP, 再生, 大肠癌

Abstract:

The intestine is an important digestive organ. Intestinal diseases such as acute or chronic enteritis and colorectal cancer pose a great threat to human health, which endows the studies related to intestine with great scientific and clinical value. The Hippo signaling pathway plays an important role in proliferation and differentiation of intestinal stem cells, and is involved in diverse physiological and pathological processes in the intestine. In this review, we summarize known functions and mechanisms of the Hippo signaling pathway in intestinal regeneration and tumorigenesis, provide a prospective on future research directions, and discuss potential therapeutic strategies targeting the Hippo signaling pathway.

Key words: intestine, Hippo signaling pathway, YAP, regeneration, colorectal cancer

顾远, 张雷, 余发星. Hippo信号通路在肠道稳态、再生及癌变过程中的作用及机制[J]. 遗传, 2017, 39(7): 588-596.

Yuan Gu, Lei Zhang, Faxing Yu. Functions and regulations of the Hippo signaling pathway in intestinal homeostasis, regeneration and tumorigenesis[J]. Hereditas(Beijing), 2017, 39(7): 588-596.

参考文献

[1]	Gardner WD, Osburn WA. Anatomy of the Human Body. 3rd ed. Philadelphia: Saunders, 1978.
[2]	van der Flier LG, Clevers H. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol, 2009, 71(1): 241-260.
[3]	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65(2): 87-108.
[4]	Yu FX, Zhao B, Guan KL. Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell, 2015, 163(4): 811-828.
[5]	Wang Y, Yu AJ, Yu FX. The Hippo pathway in tissue homeostasis and regeneration. Protein Cell, 2017, doi: 10.1007/s13238-017-0371-0.
[6]	Heath JP. Epithelial cell migration in the intestine. Cell Biol Int, 1996, 20(2): 139-146.
[7]	Sato T, Van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M, Barker N, Shroyer NF, van de Wetering M, Clevers H. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature, 2011, 469(7330): 415-418.
[8]	Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature, 2009, 459(7244): 262-265.
[9]	Mu?oz J, Stange DE, Schepers AG, van de Wetering M, Koo BK, Itzkovitz S, Volckmann R, Kung KS, Koster J, Radulescu S, Myant K, Versteeg R, Sansom OJ, van Es JH, Barker N, van Oudenaarden A, Mohammed S, Heck AJR, Clevers H. The Lgr5 intestinal stem cell signature: Robust expression of proposed quiescent ‘+4’ cell markers. EMBO J, 2012, 31(14): 3079-3091.
[10]	Tian H, Biehs B, Warming S, Leong KG, Rangell L, Klein OD, de Sauvage FJ. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature, 2011, 478(7368): 255-259.
[11]	Korinek V, Barker N, Moerer P, Van Donselaar E, Huls G, Peters PJ, Clevers H. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Tcf-4. Nat Genet, 1998, 19(4): 379-383.
[12]	Pinto D, Gregorieff A, Begthel H, Clevers H. Canonical wnt signals are essential for homeostasis of the intestinal epithelium. Genes Dev, 2003, 17(14): 1709-1713.
[13]	Fevr T, Robine S, Louvard D, Huelsken J. Wnt/β-catenin is essential for intestinal homeostasis and maintenance of intestinal stem cells. Mol Cell Biol, 2007, 27(21): 7551-7559.
[14]	Kim KA, Kakitani M, Zhao JS, Oshima T, Tang T, Binnerts M, Liu Y, Boyle B, Park E, Emtage P, Funk WD, Tomizuka K. Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science, 2005, 309(5738): 1256-1259.
[15]

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

Hippo信号通路在肠道稳态、再生及癌变过程中的作用及机制

Functions and regulations of the Hippo signaling pathway in intestinal homeostasis, regeneration and tumorigenesis

RichHTML

PDF (PC)

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics