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• W4387369901 abstract "<div>Abstract<p>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 BRAF^V600E. 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 <i>in vivo</i>. These data suggest that GABAergic signaling across the skin microenvironment regulates the ability of oncogenes to initiate melanoma.</p>Significance:<p>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.</p><p><i><a href=https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-23-0843 target=_blank>See related commentary by Ceol, p. 2128.</a></i></p><p><i><a href=https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-13-10-ITI target=_blank>This article is featured in Selected Articles from This Issue, p. 2109</a></i></p></div>" @default.
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• W4387369901 date "2023-10-05" @default.
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• W4387369901 title "Data from GABA Regulates Electrical Activity and Tumor Initiation in Melanoma" @default.
• W4387369901 doi "https://doi.org/10.1158/2159-8290.c.6866738" @default.
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