GABA-GABA_A Receptor Signaling Orchestrates Invasion and Metastasis in Triple Negative Breast Cancer

Cancer is a leading cause of death globally, with the majority of cancer-related deaths resulting from cancer metastasis -the process by which cancer cells disseminate to distant sites. While our understanding of cancer cell metastasis has advanced considerably, appreciably more work is needed. To metastasize, cancer cells acquire traits in support of diverse cellular processes that enable, dissemination, survival and colonization. Tumor cell dissemination requires invasion at local and distant sites. This process can be influenced by intrinsic and extrinsic factors. Here, we investigate the role of neurotransmitter gamma-aminobutyric acid (GABA) in triple-negative breast cancer (TNBC) invasion and metastasis. TNBC cells increased invasion in response to GABA through the GABAA receptor family -specifically GABRE- and increased GSK3α activity. TNBC cell lines were found to be responsive to exogenous GABA and also produced endogenous GABA. Blocking the actions of GABA reduced invasion and tumor cell dissemination. These findings support a role for GABA signaling through GABAA receptors in mediating the dissemination of TNBC cells.