Abstract
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 EMT and regulate the Notch1 signaling pathway. Taken together,LGR5 may have an important role in the promotion of tumorigenesis and metastasis of EOC and is a potential therapeutic target for EOC management.
Highlights
Epithelial ovarian cancer (EOC) is the most common histological type of ovarian cancer, accounting for 80% to 90% of malignancies
Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), which belongs to the G protein-coupled receptor family of proteins, is recognized as a stem cell marker of the intestinal epithelium and the hair follicle [6, 7], and has been identified as an oncogene in various cancers, including colorectal cancer [24], cervical cancer [25], neuroblastoma [26], and ovarian cancer [9]
We observed that LGR5 was overexpressed in EOC cell lines and tissues
Summary
Epithelial ovarian cancer (EOC) is the most common histological type of ovarian cancer, accounting for 80% to 90% of malignancies. EOC is the most lethal of malignant tumors of the female reproductive system [1]. The prognosis for patients suffering from ovarian cancer remains poor because of limited therapeutic strategies and late diagnosis. It is estimated that over 70% of patients are diagnosed at an advanced stage of disease, and only approximately 30% of patients survive for 5 years or more [2]. The detailed pathogenesis of EOC remains elusive.
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