The intestinal stem cell as a target: A review

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.