title: 2,2',4,4'-Tetrabromodiphenyl ether promotes human neuroblastoma SH-SY5Y cells migration via the GPER/PI3K/Akt signal pathway.
abstract: Neuroblastoma is the predominant tumor of early childhood. 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) has the highest concentration among all polybrominated diphenyl ether (PBDE) congeners in human body, particularly for children. Considering that accumulating evidences showed developmental neurotoxicity of PBDE, there is an urgent need to investigate the effects of BDE-47 on the development of neuroblastoma. This study revealed that BDE-47 had limited effects on the cytotoxicity while significantly increased the in vitro migration and invasion of human neuroblastoma SH-SY5Y cells. This was further confirmed by the results that BDE-47 treatment significantly downregulated the expression of E-cadherin and zona occludin-1 and upregulated the expression of matrix metalloproteinase-9 (MMP-9). Silencing of MMP-9 by specific small interfering RNA significantly abolished the BDE-47-induced migration and invasion of SH-SY5Y cells. Further, the signals G protein-coupled estrogen receptor 1 (GPER)/phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt) mediated the BDE-47-induced upregulation of MMP-9 and in vitro migration of SH-SY5Y cells since G15 (GPER inhibitor) and LY 294002 (PI3K/Akt inhibitor) significantly abolished the effects of BDE-47. Our results revealed that BDE-47 significantly triggered the metastasis of human neuroblastoma SH-SY5Y cells via upregulation of MMP-9 by the GPER/PI3K/Akt signal pathway. This study revealed for the first time that BDE-47 can promote the migration of SH-SY5Y cells. It also provided a better understanding about the metastasis of human neuroblastoma induced by environmental endocrine disruptors.
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: P-C
authors.initials: PC
authors.lastname: Tian
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: H-L
authors.initials: HL
authors.lastname: Wang
authors.affiliation: Department of Neurology, Zhengzhou Children's Hospital, Zhengzhou, China.
authors.forename: G-H
authors.initials: GH
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China yfliuzzu@163.com.
authors.forename: Y-F
authors.initials: YF
authors.lastname: Liu
mesh_terms: D001932:Brain Neoplasms / Q000473:pathology*; D015820:Cadherins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D002273:Carcinogens / Q000633:toxicity*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009447:Neuroblastoma / Q000473:pathology*; D051058:Oncogene Protein v-akt / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects*; D011960:Receptors, Estrogen / Q000187:drug effects*; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D062826:Zonula Occludens-1 Protein / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics
chemical_list: D015820:Cadherins; D002273:Carcinogens; D052244:Endocrine Disruptors; C109584:GPER1 protein, human; D055768:Halogenated Diphenyl Ethers; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C511295:2,2',4,4'-tetrabromodiphenyl ether; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D020780:Matrix Metalloproteinase 9
keywords: BDE-47; MMP-9; SH-SY5Y; invasion; migration