GABAergic signaling contributes to tumor cell invasion and poor overall survival in colorectal cancer.

ABSTRACT: Alterations in neurotransmitter signaling can influence colorectal cancer (CRC). In a large, randomized Phase III clinical trial (CALGB/SWOG 80405) involving patients with metastatic CRC, high expression of gamma-aminobutyric acid (GABA) pathway gene GAD1 and low expression of ABAT, indicative of a GABAergic environment, were associated with worse progression-free survival and overall survival outcomes. A metastasis map of human cancer cell lines (MetMap) and functional studies using a microfluidic tumor-on-chip platform demonstrated that high GAD1 expression correlates with increased metastatic potential. Knockdown and pharmacological inhibition of GAD1 reduced tumor invasion, while exogenous GABA promoted invasion. Tumor-derived GABA was elevated in Ras-altered tumors. Furthermore, analy

SUBMITTER: Strelez C 

PROVIDER: S-EPMC12500471 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature