Journal
CANCER MEDICINE
Volume 12, Issue 13, Pages 14498-14510Publisher
WILEY
DOI: 10.1002/cam4.6102
Keywords
cancer; carcinogenesis; GABA; GABA receptor; neurotransmitter
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GABA is the main inhibitory neurotransmitter in the brain, and it regulates tumor development via several pathways. GABA signaling exists in the cancer microenvironment and has an immunosuppressive effect that contributes to metastasis and colonization.
Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain of adult mammals. Several studies have demonstrated that the GABAergic system may regulate tumor development via GABA receptors, downstream cyclic adenosine monophosphate (cAMP) pathway, epithelial growth factor receptor (EGFR) pathway, AKT pathway, mitogen-activated protein kinase (MAPK) or extracellular signal-related kinases (ERK) pathway, and matrix metalloproteinase (MMP) pathway, although the exact mechanism is unclear. Pioneering studies reported that GABA signaling exists and functions in the cancer microenvironment and has an immunosuppressive effect that contributes to metastasis and colonization. This article reviews the molecular structures and biological functions of GABAergic components correlated with carcinogenesis, the mechanisms underlying GABAergic signaling that manipulate the proliferation and invasion of cancer cells, and the potential GABA receptor agonists and antagonists for cancer therapy. These molecules may provide an avenue for the development of specific pharmacological components to prevent the growth and metastasis of various cancers.
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