The novel estrogen receptor GPER regulates the migration and invasion of ovarian cancer cells

Abstract

G protein-coupled estrogen receptor (GPER) was identified as a new member of the estrogen receptor family in recent years. It has become apparent that GPER mediates the non-genomic signaling of 17β-estradiol (E2) in a variety of estrogen-related cancers. Our previous study has found that GPER was overexpressed in human epithelial ovarian cancer and was positively correlated with the expression of matrix metalloproteinase 9 (MMP-9), which suggested GPER might promote the metastasis of ovarian cancer. However, the mechanisms underlying GPER-dependent metastasis of ovarian cancer are still not clear. In the present study, estrogen receptor α (ERα)-negative/GPER-positive OVCAR5 ovarian cancer cell line was used to investigate the role of GPER in the migration and invasion of ovarian cancer. Wound healing assay and transwell matrigel invasion assay were performed to determine the potentials of cell migration and invasion, respectively. The production and activity of MMP-9 in OVCAR5 cells were examined by Western blot and gelatin zymography analysis. The results showed that E2 and selective GPER agonist G-1 increased cell motility and invasiveness, and upregulated the production and proteolytic activity of MMP-9 in OVCAR5 cells. Small interfering RNA (siRNA) targeting GPER and G protein inhibitor pertussin toxin (PTX) inhibited the migration and invasion of OVCAR5 cells, and also reduced the expression and activity of MMP-9. Our data suggested that GPER promoted the migration and invasion of ovarian cancer cells by increasing the expression and activity of MMP-9. GPER might play an important role in the progression of ovarian cancer.

G Protein–Coupled Estrogen Receptor Regulates Mammary Tumorigenesis and Metastasis

“…We demonstrated that KO/PyMT mice have fewer metastases compared with WT/PyMT mice, indicating that GPER plays a role in mammary tumor cell metastasis consistent with previous in vitro (16, 44, 50, 51) and clinical data (20). Several possible mechanisms have been observed for GPER-dependent tumor cell migration and invasion.…”

Rethinking tamoxifen in the management of melanoma: New answers for an old question

“…ER, estrogen receptor; GPER, G-protein coupled estrogen receptor; IGF-1R, insulin-like growth factor-1; PKCα, protein kinase C-α. estrogen receptor was shown to promote the proliferation and invasive behavior of several cancer cell lines, including breast (Girgert et al, 2012;Li et al, 2013;Pandey et al, 2009), endometrial (Du et al, 2012He et al, 2009;Ignatov et al, 2010;Vivacqua et al, 2006a), ovarian (Yan et al, 2013) and thyroid (Vivacqua et al, 2006b) cancer cells. Paradoxically, the G protein coupled estrogen receptor was also shown to mediate the inhibition of cancer cell proliferation, namely breast (Ariazi et al, 2010) and prostate cancer cells (Chan et al, 2010).…”

Estrogen-dependent expression and subcellular localization of the tight junction protein claudin-4 in HEC-1A endometrial cancer cells

“…The effects of estradiol (E 2 ) on reproductive tract structure and function are well known. Recently, however, studies have indicated a role for E 2 in tumor initiation and progression through its promotion of the proliferative, migratory and invasive capabilities of cells (2)(3)(4)(5)(6). Many of the changes that occur in the endometrium during tumorigenesis are similar to those observed during implantation.…”