LGR5 promotes the proliferation and tumor formation of cervical cancer cells through the Wnt/β-catenin signaling pathway

Abstract

Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a seven transmembrane receptor known as a potential stem cell marker for intestinal crypts and hair follicles, has recently been found to be overexpressed in some types of human cancers. However, the role of LGR5 in cervical cancer remains unclear. In this study, the expression of LGR5 gradually increases from normal cervix to cervical cancer in situ and to cervical cancers as revealed by immunohistochemistry and western blot analyses. Through knocking down or overexpressing LGR5 in SiHa and HeLa cells, the expression level of LGR5 was found to be positively related to cell proliferation in vitro and to tumor formation in vivo. Further investigation indicated that LGR5 protein could significantly promote the acceleration of cell cycle. Moreover, the TOP-Flash reporter assay and western blot for β-catenin, cyclinD1, and c-myc proteins, target genes of the Wnt/β-catenin pathway, indicated that LGR5 significantly activated Wnt/β-catenin signaling. Additionally, the blockage of Wnt/β-catenin pathway resulted in a significant inhibition of cell proliferation induced by LGR5. Taken together, these results demonstrate that LGR5 can promote proliferation and tumor formation in cervical cancer cells by activating the Wnt/β-catenin pathway.

SW480 colorectal cancer cells that naturally express Lgr5 are more sensitive to the most common chemotherapeutic agents than Lgr5-negative SW480 cells

“…The mechanism of sensitization by Lgr5 needs further investigation. Most likely Lgr5 makes cells more vulnerable to chemotherapy by increasing their propensity to divide through activation of the Wnt/β-catenin pathway [18]. In our experiments, Lgr5 promotes cell adhesion, which was shown earlier with another CRC cell line [19].…”

Early detection of biomarkers for circulating tumor cells in Bone marrow and Peripheral blood in a fast-progressing gastric cancer model

“…Of all these CSC markers, Lgr5 and CD44 are well known targets of the Wnt signaling pathway and have been implicated in cancer invasion and metastasis through their involvement in tumor formation and proliferation [85][86][87]. Lgr5 induces the Wnt/ -catenin pathway enhancing tumor formation and cancer cell proliferation [85]. The gradual increase in expression of Lgr5 we observed in our study was similar to that observed for cervical cancer [85].…”

“…and for is its role in metastasis in these cancers [84]. Of all these CSC markers, Lgr5 and CD44 are well known targets of the Wnt signaling pathway and have been implicated in cancer invasion and metastasis through their involvement in tumor formation and proliferation [85][86][87]. Lgr5 induces the Wnt/ -catenin pathway enhancing tumor formation and cancer cell proliferation [85].…”

LGRs receptors as peculiar GPCRs involved in cancer

“…In ovarian, breast and lung cancer cells, high expression of LGR5 has been correlated with advanced stages, poor overall survival and metastasis [103][104][105][106]. In cervical cancer, LGR5 promotes proliferation and tumor formation through Wnt/β-catenin signaling [107].…”