Radtke Freddy, Clevers Hans, Riccio Orbicia
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
Curr Mol Med. 2006 May;6(3):275-89. doi: 10.2174/156652406776894527.
The mammalian intestine has one of the highest turnover rates in the body. The intestinal epithelium is completely renewed in less than a week. It is divided into spatially distinct compartments in the form of finger-like projections and invaginations that are dedicated to specific functions. Intestinal cells are constantly produced from a stem cell reservoir that gives rise to proliferating transient amplifying cells, which subsequently differentiate and migrate to the correct compartment before dying after having fulfilled their physiological function. In recent years, a substantial body of evidence has accumulated to support the concept that signaling pathways known to be crucial for embryonic development of multiple organisms play a critical role in tightly regulating and controlling the self-renewing process of the intestine. Moreover, the same pathways appear to be deregulated in several hereditary and sporadic colorectal cancer syndromes due to activating and/or inactivating mutations of key components of such pathways. In this review we discuss recent findings demonstrating that differentiation and homeostasis of the intestine are controlled by developmental pathways such as Wnt, Notch, TGF-beta and Hedgehog, and illustrate how their deregulation contributes to intestinal neoplasia.
哺乳动物的肠道是体内更新速度最快的器官之一。肠道上皮细胞在不到一周的时间内就会完全更新。它以指状突起和内陷的形式分为空间上不同的隔室，这些隔室具有特定的功能。肠道细胞不断地从干细胞库中产生，干细胞库产生增殖的瞬时扩增细胞，这些细胞随后分化并迁移到正确的隔室，在完成其生理功能后死亡。近年来，大量证据积累起来支持这样一种观点，即已知对多种生物体胚胎发育至关重要的信号通路在严格调节和控制肠道的自我更新过程中起着关键作用。此外，由于这些信号通路关键成分的激活和/或失活突变，相同的信号通路在几种遗传性和散发性结直肠癌综合征中似乎失调。在这篇综述中，我们讨论了最近的研究结果，这些结果表明肠道的分化和稳态受Wnt、Notch、TGF-β和Hedgehog等发育信号通路的控制，并阐述了它们的失调如何导致肠道肿瘤形成。
