Lung Adenocarcinoma Promotes NETosis via the NPM1–TNFAIP6–CD44–SPP1 Axis
Renwang Liu, Zixuan Hu, Mingbiao Li, Shen Yang, Jianfang Wang, Zhanrui Zhang, Long Yang, Jun Chen
Journal：Cancers
IF：4.4
DOI：10.3390/cancers18061023
PMID：
Published：2026-03-22
research field：肿瘤学分子生物学细胞信号传导癌症生物学免疫学
Abstract
Simple Summary Neutrophil extracellular traps (NETs) promote cancer progression, but the regulatory mechanism underlying their formation remains unclear. This study shows that tumor necrosis factor alpha-inducible protein 6 (TNFAIP6) derived from lung adenocarcinoma induces NET formation (NETosis) in vitro and in vivo. TNFAIP6 interacts with CD44, leading to increased extracellular secreted phosphoprotein 1 (SPP1) levels and subsequent NETosis. Additionally, nucleophosmin 1 (NPM1) upregulates the transcriptional activation of TNFAIP6 by interacting with the −2000 to −1700 bp region of its promoter. Together, these results indicate that the NPM1–TNFAIP6–CD44–SPP1 axis is a critical regulator of NETosis in lung adenocarcinoma, highlighting this pathway as a potential therapeutic target for suppressing tumor progression.
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