title: Activation of G protein coupled estrogen receptor (GPER) promotes the migration of renal cell carcinoma via the PI3K/AKT/MMP-9 signals.
abstract: Renal cell carcinoma (RCC) is the third most frequent malignancy within urological oncology. However, the mechanisms responsible for RCC metastasis are still needed further illustration. Our present study revealed that a seven-transmembrane receptor G-protein coupled estrogen receptor (GPER) was highly detected in various RCC cell lines such as ACHN, OS-RC-2 and SW839. The activation of GPER by its specific agonist G-1 significantly promoted the in vitro migration and invasion of ACHN and OS-RC-2 cells. G-1 also up regulated the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. The inhibitor of MMP-9 (Cat-444278), but not MMP-2 (Sc-204092), abolished G-1 induced cell migration, which suggested that MMP-9 is the key molecule mediating G-1 induced RCC progression. Further, G-1 treatment resulted in phosphorylation of AKT and ERK in RCC cells. PI3K/AKT inhibitor (LY294002), while not ERK inhibitor (PD98059), significantly abolished G-1 induced up regulation of MMP-9 in both AHCN and OS-RC-2 cells. Generally, our data revealed that activation of GPER by its specific agonist G-1 promoted the metastasis of RCC cells through PI3K/AKT/MMP-9 signals, which might be a promising new target for drug discovery of RCC patients.
authors.affiliation: a Department of Nephrology , The First Affiliated Hospital of Jinan University , Guangzhou , China.|c The authors contributed equally to this work.
authors.forename: Bao-Zhang
authors.initials: BZ
authors.lastname: Guan
authors.affiliation: b Department of Gynecotokology , The First Affiliated Hospital of Jinan University , Guangzhou , China.|c The authors contributed equally to this work.
authors.forename: Rui-Ling
authors.initials: RL
authors.lastname: Yan
authors.affiliation: a Department of Nephrology , The First Affiliated Hospital of Jinan University , Guangzhou , China.
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Huang
authors.affiliation: a Department of Nephrology , The First Affiliated Hospital of Jinan University , Guangzhou , China.
authors.forename: Fo-Lan
authors.initials: FL
authors.lastname: Li
authors.affiliation: a Department of Nephrology , The First Affiliated Hospital of Jinan University , Guangzhou , China.
authors.forename: Ying-Xue
authors.initials: YX
authors.lastname: Zhong
authors.affiliation: a Department of Nephrology , The First Affiliated Hospital of Jinan University , Guangzhou , China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: a Department of Nephrology , The First Affiliated Hospital of Jinan University , Guangzhou , China.
authors.forename: Fan-Na
authors.initials: FN
authors.lastname: Liu
authors.affiliation: a Department of Nephrology , The First Affiliated Hospital of Jinan University , Guangzhou , China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: a Department of Nephrology , The First Affiliated Hospital of Jinan University , Guangzhou , China.
authors.forename: Si-Bo
authors.initials: SB
authors.lastname: Huang
authors.affiliation: a Department of Nephrology , The First Affiliated Hospital of Jinan University , Guangzhou , China.
authors.forename: Liang-Hong
authors.initials: LH
authors.lastname: Yin
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000819:agonists*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D020780:Matrix Metalloproteinase 9; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D011960:Receptors, Estrogen; C506487:ESR1 protein, human; C579270:MMP9 protein, human
keywords: G-1; GEPR; MMP-9; PI3K/AKT; renal cell carcinoma