Notch as a Driver of Gastric Epithelial Cell Proliferation.
Notch as a Driver of Gastric Epithelial Cell Proliferation.
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DOI：
10.1016/j.jcmgh.2017.01.012
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发表时间：
2017-05
影响因子：
7.2
通讯作者：
Samuelson LC
中科院分区：
文献类型：
--
作者：
Demitrack ES;Samuelson LC
胃上皮由一群干细胞维持，这些干细胞在整个成年期补充各种成熟的上皮谱系。干细胞和祖细胞增殖的调节通过基本的发育信号传导途径发生，包括Notch途径，其最近被描述为促进小鼠和人类的胃干细胞增殖。目前的癌症理论认为，维持胃肠道组织的成体干细胞积累了促进癌细胞生长的突变，并且刺激干细胞增殖的基本信号传导途径（如Notch）可以促进肿瘤发生。因此，组成型Notch活化导致遗传小鼠模型中未受抑制的细胞增殖和胃肿瘤。此外，有新的证据表明，Notch途径可能在一些人胃癌中被激活，支持Notch在胃肿瘤发生中的潜在作用。在这篇综述中，我们首先总结了目前的理解胃干细胞定义的遗传小鼠的研究，其次是有关Notch途径调节胃干细胞功能的文献在小鼠和人类的讨论。Notch的行动，以维持胃上皮细胞的稳态和失调的信号传导，以促进肿瘤发生的细胞后果进行了讨论，包括研究与人类胃癌Notch激活。最后，我们将Notch在胃中的功能与其他胃肠道组织（包括肠）进行比较和对比，以突出胃对Notch诱导的肿瘤的敏感性。
The gastric epithelium is sustained by a population of stem cells that replenish the various mature epithelial lineages throughout adulthood. Regulation of stem and progenitor cell proliferation occurs via basic developmental signaling pathways, including the Notch pathway, which recently was described to promote gastric stem cell proliferation in both mice and human beings. Current cancer theory proposes that adult stem cells that maintain gastrointestinal tissues accumulate mutations that promote cancerous growth, and that basic signaling pathways, such as Notch, which stimulate stem cell proliferation, can promote tumorigenesis. Accordingly, constitutive Notch activation leads to unchecked cellular proliferation and gastric tumors in genetic mouse models. Furthermore, there is emerging evidence suggesting that the Notch pathway may be activated in some human gastric cancers, supporting a potential role for Notch in gastric tumorigenesis. In this review, we first summarize the current understanding of gastric stem cells defined by genetic mouse studies, followed by discussion of the literature regarding Notch pathway regulation of gastric stem cell function in the mouse and human beings. Notch action to maintain gastric epithelial cell homeostasis and the cellular consequences of dysregulated signaling to promote tumorigenesis are discussed, including studies associating Notch activation with human gastric cancer. Finally, we compare and contrast Notch function in the stomach with other gastrointestinal tissues, including the intestine, to highlight the sensitivity of the stomach to Notch-induced tumors.