Expression and functional analyses of G protein-coupled receptor GPR49/LGR5 in human tissues and diseases

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GPR49/LGR5 is reportedly expressed in stem cells of the intestinal crypts and hair follicles of mice, and is overexpressed in some types of cancer. We showed that there was significant overexpression of LGR5 in 35 of 50 colorectal cancers, and in all sporadic colonic adenomas, compared with matched normal mucosa. LGR5 expression correlated significantly with lymphatic invasion, vascular invasion, tumor depth, lymph node metastasis, and tumor stage(IIIC vs. IIIB). In addition to cancer cells, crypt base columnar cells of the small intestine and colon were shown by in situ hybridization to express LGR5. This is the first report suggesting the involvement of LGR5, not only in early events but also in late events in colorectal tumorigenesis. We also overexpressed or down-regulated LGR5 expression in HCC cell lines to explore the function of LGR5 in cancer cells. In vivo and in vitro data suggested that aberrant expression of LGR5 regulates epithelial cell phenotype and survival