LGR5 promotes epithelial ovarian cancer proliferation metastasis and epithelial–mesenchymal transition through the Notch1 signaling pathway

摘要

Leucine‐rich repeat‐containing G protein‐coupled receptor 5 (LGR5) 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 LGR5 in human EOC. We evaluated LGR5 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 LGR5 was overexpressed in EOC tissues and cell lines. Aberrant expression of LGR5 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 LGR5 expression led to decreased proliferation and metastasis of EOC cell lines. Furthermore, LGR5 could induce style="fixed-case">EMT and regulate the Notch1 signaling pathway. Taken together, style="fixed-case">LGR5 may have an important role in the promotion of tumorigenesis and metastasis of style="fixed-case">EOC and is a potential therapeutic target for style="fixed-case">EOC management.