title: GABAergic signaling facilitates breast cancer metastasis by promoting ERK1/2-dependent phosphorylation.
abstract: The present study aims to determine the role of γ-aminobutyric acid (GABA) signaling molecules in breast cancer metastasis. Our results reveal that GABAergic system exists in breast cancer cells. Both the GABA synthetic enzyme. (GAD65/67) and GABAB receptor are expressed in 4T1 mouse breast cancer cells, MCF-7 human breast cancer cells and human breast cancer tissue. Baclofen, a GABABR agonist, significantly promoted 4T1 cells invasion and migration in vitro and metastasis in vivo, an event that was attenuated by GABABR antagonist CGP55845. Baclofen-induced breast cancer metastasis was mediated by ERK1/2 pathway.
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan 250012, China.
authors.forename: Depu
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan 250012, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan 250012, China.
authors.forename: Ziming
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan 250012, China.
authors.forename: Chuanfei
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan 250012, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Ning
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan 250012, China. Electronic address: ljingxin@sdu.edu.cn.
authors.forename: Jingxin
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000556:secondary*; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; C535150:MAPK1 protein, human; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2
keywords: Breast cancer; ERK; GABA receptor; Metastasis; γ-Aminobutyric acid