LGR5 promotes the proliferation and tumor formation of cervical cancer cells through the Wnt/β-catenin signaling pathway
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Qing Chen1,2, Hao-Zhe Cao1 and Peng-Sheng Zheng1,2,3
1 Department of Reproductive Medicine, the First Affiliated Hospital, Xi’an Jiaotong University Medical School, Xi’an, the People’s Republic of China
2 Department of Biochemistry and Molecular Biology, Xi’an Jiaotong University Medical School, Xi’an, the People’s Republic of China
3 Division of Cancer Stem Cell Research, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an Jiaotong University Medical School, Xi’an, the People’s Republic of China
Peng-Sheng Zheng, email:
Keywords: LGR5, cervical cancer, proliferation, cell cycle, Wnt/β-catenin signaling
Received: June 17, 2014 Accepted: August 20, 2014 Published: August 21, 2014
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.
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