title: GPER/ERK&AKT/NF-κB pathway is involved in cadmium-induced proliferation, invasion and migration of GPER-positive thyroid cancer cells.
abstract: The higher incidence of thyroid cancer in women during reproductive years compared with men and the increased risk associated with the therapeutic use of estrogen have strongly suggested that estrogen may be involved in the occurrence and development of thyroid cancer. Cadmium (Cd) is a potent metalloestrogen that disrupts the endocrine system by mimicking the effects of 17β-estradiol (E2). In the present study, we demonstrate that similar to E2 and G1, a specific agonist for G protein-coupled estrogen receptor (GPER), Cd induces the proliferation, invasion and migration of human WRO and FRO thyroid cancer cells that have endogenous GPER. Moreover, like E2 and G1, Cd leads to a rapid activation of ERK/AKT, and then nuclear translocation of NF-κB, increased expression of cyclin A and D1, and secretion of IL-8, all of which are significantly attenuated by GPER blockage or knock-down in both WRO and FRO cells. Furthermore, the Cd-induced proliferation, invasion and migration are suppressed either by specific inhibitors for GPER, ERK, AKT and NF-κB, or by knock-down of GPER. These results suggest that GPER/ERK&AKT/NF-κB signaling pathway is involved in the Cd-induced proliferation, invasion and migration of GPER-positive thyroid cancer cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
authors.forename: Ling-Yao
authors.initials: LY
authors.lastname: Liao
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Mo
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong, China.
authors.forename: George G
authors.initials: GG
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China. Electronic address: liuzm9999@aliyun.com.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002104:Cadmium / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D019925:Cyclin A / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D019925:Cyclin A; D004967:Estrogens; C109584:GPER1 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D002104:Cadmium; D019938:Cyclin D1; D004958:Estradiol; D051057:Proto-Oncogene Proteins c-akt
keywords: Cadmium; GPER; Invasion; Migration; Proliferation; Thyroid cancer