ArticleCancer discovery2023
GABA Regulates Electrical Activity and Tumor Initiation in Melanoma.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 40 citations in OpenAlex.
- The CAGE Framework (Calcium-Gated Excitability): From Single Neurotransmitters to Calcium States in the Tumor Microenvironment.International journal of molecular sciences · 2026Review
- Beyond the Brain: GABAergic Signaling as a Peripheral Modulator of Skin Barrier Immunity.International journal of molecular sciences · 2026Review
- Abnormally Elevated PKCδ Delays Diabetic Wound Healing by Inhibiting the GAD1-GABA Pathway.Diabetes & metabolism journal · 2026Article
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- Article
- Gamma-aminobutyric acid transaminase mediates tumor suppression in renal cell carcinoma through the cGAS-STING-interferon-β axis.Scientific reports · 2026Article
- The Neuro-Melanoma Singularity: Convergent Evolution of Neural and Melanocytic Networks in Brain Metastatic Adaptation.Biomolecules · 2025Review
- Article
- Neurotransmitters in tumors: chemical cross-talk shaping tumor progression.Biomarker research · 2025Review
- USP5-Mediated PD-L1 deubiquitination regulates immunotherapy efficacy in melanoma.Journal of translational medicine · 2025Article
- Crosstalk in Skin: Loss of Desmoglein 1 in Keratinocytes Inhibits BRAFThe Journal of investigative dermatology · 2025Article
- The SWI/SNF PBAF complex facilitates REST occupancy at repressive chromatin.Molecular cell · 2025Article
- Desmosome mutations impact the tumor microenvironment to promote melanoma proliferation.Nature genetics · 2025Article
- GABRD Accelerates Tumour Progression via Regulating CCND1 Signalling Pathway in Gastric Cancer.Journal of cellular and molecular medicine · 2025Article
- GABA regulates metabolic reprogramming to mediate the development of brain metastasis in non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Neuronal mimicry in tumors: lessons from neuroscience to tackle cancer.Cancer metastasis reviews · 2025Review
- Bioelectricity is a universal multifaced signaling cue in living organisms.Molecular biology of the cell · 2025Review
- Neuroscience of cancer: unraveling the complex interplay between the nervous system, the tumor and the tumor immune microenvironment.Molecular cancer · 2025Review
- The double role of GABAergic system in systemic tumors: an updated review.Frontiers in oncology · 2025Review
- Targeting GABA signaling in the tumor microenvironment: implications for immune cell regulation and immunotherapy resistance.Frontiers in immunology · 2025Review
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
Oncogenes can initiate tumors only in certain cellular contexts, which is referred to as oncogenic competence. In melanoma, whether cells in the microenvironment can endow such competence remains unclear. Using a combination of zebrafish transgenesis coupled with human tissues, we demonstrate that GABAergic signaling between keratinocytes and melanocytes promotes melanoma initiation by BRAFV600E. GABA is synthesized in melanoma cells, which then acts on GABA-A receptors in keratinocytes. Electron microscopy demonstrates specialized cell-cell junctions between keratinocytes and melanoma cells, and multielectrode array analysis shows that GABA acts to inhibit electrical activity in melanoma/keratinocyte cocultures. Genetic and pharmacologic perturbation of GABA synthesis abrogates melanoma initiation in vivo. These data suggest that GABAergic signaling across the skin microenvironment regulates the ability of oncogenes to initiate melanoma. SIGNIFICANCE: This study shows evidence of GABA-mediated regulation of electrical activity between melanoma cells and keratinocytes, providing a new mechanism by which the microenvironment promotes tumor initiation. This provides insights into the role of the skin microenvironment in early melanomas while identifying GABA as a potential therapeutic target in melanoma. See related commentary by Ceol, p. 2128. This article is featured in Selected Articles from This Issue, p. 2109.
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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.