Activation Of GABA_B Receptor Inhibited Epithelial-Mesenchymal Transition Of Human Breast Carcinoma Cell Line MDA-MB-231

γ-Aminobutyric acid (GABA) is the most important inhibitory neurotransmitter inthe adult mammalian brain. The effects of GABA are mediated by either ionotropic(GABAAor GABAC) or metabotropic (GABAB) receptors. Metabotropic GABABreceptorbelongs to class C G-protein coupled receptors (GPCRs) that mediate GABA response byactivating G-protein systems. GABABreceptor mediates various cellular events, such asproliferation, migration, differentiation, cell cycle, genes transcription, apoptosis andoncogenesis. GABABreceptor is involved in the regulation of important cell signalingpathways found not only in nervous system, but also in peripheral tissues and in cancertissuesBreast cancer is the second leading cause of cancer death in women with more than1.67million new cases each year in western populations in2012. Metastasis refers to thespread of cancer to distant organs in the body. More than90%of mortality associated withcancer is due to the metastasis of the original tumor. This process is responsible byepithelial mesenchymal transition (EMT) of the cells that facilitate migrations of the cellsto surrounding tissues. The aim of this study is to investigate the possibility of GABABreceptor as a therapeutic target in the treatment of metastasis of breast cancer, which hasnot been addressed yet.The present study showed that GABABreceptor activation had no significant effecton cell survival after3days of treatment with Baclofen and/or CGP7930at differentconcentrations as the MTT assay suggested. GABABreceptor activation enhancedexpression of epithelial cell marker molecule E-cadherin and supressed mesenchymal cellmarker molecule β-catenin. in vitro, resulting in decreased cell migration and invasion,suggesting that GABABreceptor might be a potential therapeutic target in metastatic breastcancer.