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肠干细胞作为靶点:综述。

The intestinal stem cell as a target: A review.

机构信息

Department of Clinical Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.

出版信息

Medicine (Baltimore). 2024 Aug 23;103(34):e39456. doi: 10.1097/MD.0000000000039456.

Abstract

Human intestinal epithelium handles several events that may affect health. It is composed of villi and crypts, which contain different types of cells. Each cell type plays an essential role in intestinal functions, including absorption, defense, self-renewal, and regeneration. Intestinal stem cells (ISCs), located at the base of intestinal crypts, play an important role in intestinal homeostasis and renewal. Any disruption in intestinal homeostasis, in which ISCs alter their function, may result in tumor growth. As Wnt and Notch signaling pathways are essential for ISCs homeostasis and for maintaining self-renewal, any defects in these pathways could increase the risk of developing colorectal cancer (CRC). Lgr5+ cells have been identified as intestinal stem cells expressing a leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), which is involved in the regulation of Wnt signaling. Several studies have reported upregulated expression of LGR5 in CRC. Hence, in this review, we discuss the relationship between LGR5, Wnt signaling, and Notch signaling and the development of CRC, as well as recent therapeutic strategies targeting LGR5, cancer stem cells (CSCs), and the aforementioned signaling pathways.

摘要

人类肠道上皮细胞处理多种可能影响健康的事件。它由绒毛和隐窝组成,其中包含不同类型的细胞。每种细胞类型在肠道功能中都起着至关重要的作用,包括吸收、防御、自我更新和再生。位于肠隐窝底部的肠干细胞(ISCs)在肠道内稳态和更新中发挥着重要作用。任何破坏肠道内稳态的行为,即 ISCs 改变其功能的行为,都可能导致肿瘤生长。由于 Wnt 和 Notch 信号通路对于 ISCs 的内稳态和维持自我更新至关重要,因此这些通路的任何缺陷都可能增加结直肠癌(CRC)的风险。Lgr5+细胞已被鉴定为表达富含亮氨酸重复的 G 蛋白偶联受体 5(LGR5)的肠干细胞,该受体参与 Wnt 信号的调节。几项研究报告称,CRC 中 LGR5 的表达上调。因此,在这篇综述中,我们讨论了 LGR5、Wnt 信号和 Notch 信号与 CRC 发展之间的关系,以及最近针对 LGR5、癌症干细胞(CSCs)和上述信号通路的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff3/11346866/4c205420e499/medi-103-e39456-g001.jpg

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