GABAergic signaling facilitates breast cancer metastasis by promoting ERK1/2-dependent phosphorylation

The present study aims to determine the role of gamma-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 GABA(B)R agonist, significantly promoted 4T1 cells invasion and migration in vitro and metastasis in vivo, an event that was attenuated by GABA(B)R antagonist CGP55845. Baclofen-induced breast cancer metastasis was mediated by ERK1/2 pathway. (C) 2014 Elsevier Ireland Ltd. All rights reserved.