title: 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.
authors.affiliation: Laboratory of Reproductive Endocrinology, Department of Physiology, Harbin Medical University, Nangang District, Harbin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.forename: Huidi
authors.initials: H
authors.lastname: Liu
authors.forename: Haixia
authors.initials: H
authors.lastname: Wen
authors.forename: Xueli
authors.initials: X
authors.lastname: Jiang
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Cao
authors.forename: Guangmei
authors.initials: G
authors.lastname: Zhang
authors.forename: Guoyi
authors.initials: G
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D004790:Enzyme Induction; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C109584:GPER1 protein, human; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9