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

被引:73
作者
Chen, Qing [1 ,2 ]
Cao, Hao-Zhe [1 ]
Zheng, Peng-Sheng [1 ,2 ,3 ]
机构
[1] Xi An Jiao Tong Univ, Sch Med, Affiliated Hosp 1, Dept Reprod Med, Xian 710049, Peoples R China
[2] Xi An Jiao Tong Univ, Sch Med, Dept Biochem & Mol Biol, Xian 710049, Peoples R China
[3] Xi An Jiao Tong Univ, Sch Med, Minist Educ, Div Canc Stem Cell Res,Key Lab Environm & Genes R, Xian 710049, Peoples R China
基金
中国国家自然科学基金;
关键词
LGR5; cervical cancer; proliferation; cell cycle; Wnt/beta-catenin signaling; PROTEIN-COUPLED RECEPTOR; STEM-CELLS; WNT RECEPTORS; IN-VITRO; MARKER; OVEREXPRESSION; IDENTIFICATION; CARCINOMAS; EXPRESSION; R-SPONDIN1;
D O I
10.18632/oncotarget.2377
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 beta-catenin, cyclinD1, and c-myc proteins, target genes of the Wnt/beta-catenin pathway, indicated that LGR5 significantly activated Wnt/beta-catenin signaling. Additionally, the blockage of Wnt/beta-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/beta-catenin pathway.
引用
收藏
页码:9092 / 9105
页数:14
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