{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE343nnn/GSE343586/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE343586"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"N-WASP deficiency enhances oncogenic KRAS-mediated lung adenocarcinoma progression in mice","description":"Objective: Oncogenic KRAS mutations drive 25-30% of western lung adenocarcinoma (LUAD) cases, however the mechanisms that restrain tumor progression remain poorly defined. N-Wiskott–Aldrich syndrome protein (N-WASP) regulates actin cytoskeleton dynamics and epithelial architecture, but its role in KRAS-driven lung tumorigenesis is unclear. Methods: We generated a conditional N-WASP knockout in KRASG12D-driven lung adenocarcinoma mice (N-WASPLKO/KRASG12D) using Sftpc-CreERT2, and assessed N-WASP knockdown A549 cells (A549KD) in 3D culture for tumor burden, ERK signaling, transcriptomic changes, and E-cadherin expression.Results: Conditional deletion of N-WASP in type II alveolar cells (N-WASPLKO) markedly increased tumor number and size in KRASG12D mice. The tumors isolated from these mice retained strong pro–surfactant protein C expression, confirming alveolar epithelial origin and predominantly adopted a solid growth pattern, indicative of disrupted epithelial organization. Mechanistically, N-WASP loss enhanced KRAS-driven ERK1/2 activation in lung tissue, consistent with increased mitogenic signaling. In A549 cells, N-WASP deficiency disrupted cytoskeletal architecture, promoted proliferation, and impaired cell–cell adhesion, recapitulating in vivo tumor phenotypes. Transcriptomic profiling of N-WASP–deficient lungs revealed coordinated upregulation of genes regulating proliferation, cytoskeletal remodeling, and tumor-promoting pathways, alongside downregulation of epithelial differentiation and adhesion programs.","dates":{"publication":"2026/09/08"},"accession":"GSE343586","cross_references":{"GSM":["GSM9957832","GSM9957830","GSM9957831","GSM9957829","GSM9957827","GSM9957828"],"GPL":["17021"],"GSE":["343586"],"taxon":["Mus musculus"]}}