The role of γ-aminobutyric acid and its receptor in metabolic reprogramming and tumor progression

Neurotransmitters play fundamental regulatory roles within the central nervous system (CNS), where they modulate neuronal signaling and maintain neural network homeostasis. Beyond their classical functions in the CNS, these signaling molecules can act on other organs throughout the body via vagus nerve terminals, mediating crosstalk between the nervous system and peripheral tissues. Notably, such neurotransmitter-mediated interorgan communication has been implicated in driving metabolic reprogramming, a key adaptive process that can promote tumor initiation and progression. Among the diverse neurotransmitters involved, γ-aminobutyric acid (GABA) has garnered increasing attention, as it exhibits elevated levels in various types of tumors. Accordingly, this review focuses on elucidating the mechanisms of GABA synthesis and secretion, while systematically investigating the role of GABA and its receptors in metabolic reprogramming and the regulation of the tumor immune microenvironment. Collectively, this work aims to unravel the multifaceted contributions of GABA to oncogenesis and thereby to offer novel therapeutic targets for cancer treatment.