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

Depu Zhang; Xiaowei Li; Ziming Yao; Chuanfei Wei; Nannan Ning; Jingxin Li

doi:10.1016/j.canlet.2014.03.006

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

Cancer Lett. 2014 Jun 28;348(1-2):100-8. doi: 10.1016/j.canlet.2014.03.006. Epub 2014 Mar 18.

Authors

Depu Zhang¹, Xiaowei Li¹, Ziming Yao¹, Chuanfei Wei¹, Nannan Ning¹, Jingxin Li²

Affiliations

¹ Department of Physiology, School of Medicine, Shandong University, Jinan 250012, China.
² Department of Physiology, School of Medicine, Shandong University, Jinan 250012, China. Electronic address: ljingxin@sdu.edu.cn.

PMID: 24657659
DOI: 10.1016/j.canlet.2014.03.006

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.

Keywords: Breast cancer; ERK; GABA receptor; Metastasis; γ-Aminobutyric acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Breast Neoplasms / enzymology*
Breast Neoplasms / pathology*
Cell Movement* / drug effects
Dose-Response Relationship, Drug
Female
GABA-B Receptor Agonists / pharmacology
GABA-B Receptor Antagonists / pharmacology
Glutamate Decarboxylase / metabolism
Humans
Lung Neoplasms / enzymology*
Lung Neoplasms / secondary*
MCF-7 Cells
Matrix Metalloproteinase 2 / metabolism
Mice
Mice, Inbred BALB C
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3 / metabolism*
Neoplasm Invasiveness
Phosphorylation
Receptors, GABA-B / drug effects
Receptors, GABA-B / metabolism
Signal Transduction* / drug effects
Time Factors
gamma-Aminobutyric Acid / metabolism*

Substances

GABA-B Receptor Agonists
GABA-B Receptor Antagonists
Receptors, GABA-B
gamma-Aminobutyric Acid
MAPK1 protein, human
Mapk1 protein, mouse
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
MMP2 protein, human
Matrix Metalloproteinase 2
Mmp2 protein, rat
Glutamate Decarboxylase
glutamate decarboxylase 1
glutamate decarboxylase 2