ArticleOncogene2025
GABAergic signaling contributes to tumor cell invasion and poor overall survival in colorectal cancer.
Article in Oncogene, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- Neuro-immune interactions in tumors, immune-related disorders, and infections.Signal transduction and targeted therapy · 2026Review
- Microphysiological models of human gastrointestinal diseases.Nature biomedical engineering · 2026Review
- Targeting the nervous system: Mechanistic insights into neuro-tumor communication and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Construction of lactate-myeloid-related prognostic risk model and prediction of immune-excluded microenvironment in gastric cancer via integrated scRNA-Seq and bulk RNA-Seq.Translational cancer research · 2026Article
- Bidirectional crosstalk between the nervous system and the tumour microenvironment: mechanisms, feedback loops and therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Integrated multi-omics reveals GABARAP-mediated mitophagy and pyruvate metabolism as key drivers of osteosarcoma progression.Frontiers in immunology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors.
Funding
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, analysis of publicly available data confirmed that higher GAD1 expression is associated with worse outcomes in Ras-mutant tumors. These findings establish a role for GABA signaling in tumor invasiveness, particularly in Ras-altered CRC. This study demonstrates using clinical data to inform new discoveries and highlights the need for advanced preclinical model systems that more accurately reflect human physiology to explore these findings.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.