Open AccessLGR 5 promotes epithelial ovarian cancer proliferation, metastasis, and epithelial–mesenchymal transition through the Notch1 signaling pathway
Author(s) -
Liu Wenxue,
Zhang Jing,
Gan Xupei,
Shen Fangqian,
Yang Xiaoming,
Du Na,
Xia Dandan,
Liu Lei,
Qiao Lianqiao,
Pan Jufang,
Sun Yunyan,
Xi Xiaowei
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1485
Subject(s) - lgr5 , epithelial–mesenchymal transition , metastasis , cancer research , carcinogenesis , ovarian cancer , cell growth , biology , western blot , cell migration , stem cell , cell , cancer stem cell , cancer , microbiology and biotechnology , biochemistry , genetics , gene
Leucine‐rich repeat‐containing G protein‐coupled receptor 5 ( LGR 5) plays a vital role in the development of malignant tumors; however, its biological role and underlying mechanism in epithelial ovarian cancer ( EOC ) remain unclear. In this study, we aimed to investigate the biological function and clinical significance of LGR 5 in human EOC . We evaluated LGR 5 expression in EOC cell lines and tissues from ovarian cancer patients by qPCR , Western blotting, and immunohistochemical analysis. Cell proliferation, colony formation, transwell invasion assay, and scratch‐wound assays were conducted to evaluate the expansion and invasion abilities of EOC cells. Tumor xenograft experiments were performed in female BALB /c athymic nude mice to test cell proliferation in vivo. Western blot analysis was performed to confirm the expression of epithelial‐to‐mesenchymal transition ( EMT ) signature proteins and their association with Notch1 signaling. The results demonstrated that LGR 5 was overexpressed in EOC tissues and cell lines. Aberrant expression of LGR 5 was significantly associated with patient age ( P = 0.006), tumor histologic type ( P < 0.001), and distant metastasis ( P = 0.025). Consistent with these findings, suppression of LGR 5 expression led to decreased proliferation and metastasis of EOC cell lines. Furthermore, LGR 5 could induce EMT and regulate the Notch1 signaling pathway. Taken together, LGR 5 may have an important role in the promotion of tumorigenesis and metastasis of EOC and is a potential therapeutic target for EOC management.