title: Role of GPER on proliferation, migration and invasion in ligand-independent manner in human ovarian cancer cell line SKOV3.
abstract: G protein-coupled estrogen receptor (GPER) is identified as a critical estrogen receptor, in addition to the classical estrogen receptors ERα and ERβ. In ERα-negative ovarian cancer cells, our previous studies have found that estrogen stimulated cell proliferation and metastasis via GPER. However, the ligand-independent function of GPER in ovarian cancer cells is still not clear. Herein, we describe that GPER has a co-expression with ERα and ERβ, which are first determined in SKOV3 ovarian cancer cell line. In the absence of estrogen, GPER depletion by specific siRNA inhibits the proliferation, migration and invasion of SKOV3 cells. Whereas abrogation of ERα or ERβ by specific antagonist MPP and PHTPP has the opposite effects for stimulation of cell growth. Markedly, GPER knockdown attenuates MPP or PHTPP-induced cell proliferation, migration and invasion. Furthermore, GPER modulates protein expression of the cell cycle critical components, c-fos and cyclin D1 and factors for cancer cell invasion and metastasis, matrix metalloproteinase 2 (MMP-2) and MMP-9. These findings establish that GPER ligand-independently stimulates the proliferation, migration and invasion of SKOV3 cells. Knockdown of GPER attenuates the progression of ovarian cancer that caused by functional loss of ERα or ERβ. Targeting GPER provides new aspect as a potential therapeutic strategy in ovarian cancer.
authors.affiliation: Laboratory of Reproductive Endocrinology, Department of Physiology, Harbin Medical University, Harbin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Laboratory of Reproductive Endocrinology, Department of Physiology, Harbin Medical University, Harbin, China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Laboratory of Reproductive Endocrinology, Department of Physiology, Harbin Medical University, Harbin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Laboratory of Reproductive Endocrinology, Department of Physiology, Harbin Medical University, Harbin, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Wen
authors.affiliation: Laboratory of Reproductive Endocrinology, Department of Physiology, Harbin Medical University, Harbin, China.
authors.forename: Guoyi
authors.initials: G
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008024:Ligands; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D059748:Proteolysis; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D034622:RNA Interference; D011960:Receptors, Estrogen / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: C109584:GPER1 protein, human; D008024:Ligands; D016760:Proto-Oncogene Proteins c-fos; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D019938:Cyclin D1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: ERα; ERβ; G protein-coupled estrogen receptor; invasion; migration; ovarian cancer; proliferation