3rd International Congress on Biomedicine (ICB2019)
Lgr5 is demonstrated as a representative marker of intestinal stem cells for colon malignancy
Lgr5 is demonstrated as a representative marker of intestinal stem cells for colon malignancy
Muhammad Sadeqi Nezhad,1,*Maryam Karami,2
1. Department of Laboratory Science, Young Researchers and Elites Club, Gorgan Branch, Islamic Azad University, Gorgan, Iran 2. Department of Biotechnology, Gorgan Branch, Islamic Azad University, Gorgan, Iran
Introduction: Despite the breakthrough in the field of oncology, there has no appropriate and promising marker of intestinal cells been designated for therapeutic and prognosis purposes. The intestinal epithelium is one of the most frequently renewing tissues in the human body, with a turnover period of 3–5 days in the small intestine. This speedy renewal of the intestinal epithelium is associated with the stem cells located at the crypt bottom, providing remarkable approach to study stem cell functions and dynamics.
Methods: After an encyclopedic online research through eminent database like Science Direct, ISI Web of Science, Scopus, and PubMed the following results were achieved.
Results: Based on the different tumor types, the cancer stem cells were identified by the expression of different markers, such as CD133+ CD166+, CD44+, CD29+, CD24+, EpCAM, Lgr5, aldehyde dehydrogenase, and a few others. Thus, leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), a seven-transmembrane spanning receptor, is identified as an ideal surface marker of intestinal stem cells which expressed during embryonic development and in adult stem cells in the colon and kidney. It has been reported that Lgr5 provides a central role in both growth and survival of cancer cells in which the overexpression was observed in several types of cancer including colorectal cancers. However, LGR5 modulates signaling through Wnt pathway upon binding to its cognate ligand R-spondin. R-spondins are a group of four secreted proteins (RSPO1 to -4) that were characterized as a potent agonists of Wnt signaling with pleiotropic functions in development, differentiation, oncogenesis, and stem cell survival. Previous studies reported that exhausted Lgr5 leads to apoptosis via the loss of mitochondrial membrane. Additionally, exhaustion of Lgr5 inhibited β-catenin nuclear translocation and suppressed the activity of Wnt/β-catenin signaling as manifested in the reduced expression of c-myc and cyclin D, two Wnt/β-catenin targets in Colorectal Cancer cells.
Conclusion: While Lgr5 considers playing a receptor role for a peptide ligand, thereby there is still hope to exert this prominent protein as a marker of intestinal cells. Moreover, Lgr5 expression was deemed to be closely associated with stemness, highlighting its role to control crucial aspects of stem cell behavior and a promising future target for colorectal cancer therapy.