BackgroundLung adenocarcinoma (LUAD) was known to have a propensity for brain metastasis. Neutrophil extracellular traps (NETs) played a role in facilitating tumor metastasis.
However, the specific role of IL-17A in triggering the formation of NETs and its impact on NETs-mediated brain metastasis in LUAD was not well understood.ObjectiveWe sought to investigate the IL-17A’s role in promoting NET formation, EMT, and brain metastasis in LUAD.MethodsWe conducted LASSO and Cox regression analyses to pinpoint the essential genes in NETs that regulate LUAD. We carried out survival assays to validate the significance of the identified key genes.
In vitro and in vivo models assessed NETs-IL17-induced EMT and metastasis, with P300’s role examined using siRNA and inhibitor B026. ChIP-qPCR and Co-IP revealed IL17A-DNA interactions and H2BC4/p300 recruitment to EMT gene promoters.ResultsIn neutrophils, IL-17A stimulation-induced NET formation may be associated with EP300-mediated increased acetylation of H2BC4.
NETs activated IL17 signaling to drive EMT and brain metastasis. NETs enhanced tumor metastasis to brain, which was significantly suppressed by PAD inhibitors or DNase I.
Frontiers in Immunology published a clinical update in Infectious Disease on 25 May 2026.
The item focuses on Mechanistic and functional characterization of NETs/IL-17 as a therapeutic target in EMT and brain metastasis of lung adenocarcinoma.
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