Genetic and drug perturbation of components in the NFkB signaling pathway in 11-18 cells
Transcriptomics Dataset
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General Information
AccessionGSE65420
TitleGenetic and drug perturbation of components in the NFkB signaling pathway in 11-18 cells
DescriptionThrough the study of EGFR-mutant lung adenocarcinoma we show that NFkB signaling is rapidly engaged by EGFR oncogene inhibition to promote tumor cell persistence and therapy resistance. Unexpectedly, we found that EGFR oncogene inhibition induced an EGFR-TRAF2-RIP1-IKK complex that stimulated an NFkB-mediated transcriptional survival program. We identified a direct pharmacologic NFkB inhibitor, PBS-1086, that suppressed this adaptive survival program and increased both the magnitude and duration of initial EGFR TKI response in cellular and in vivo tumor models, including a novel patient-derived NSCLC xenograft. These findings unveil NFkB as a critical adaptive survival mechanism engaged in response to EGFR oncogene inhibition and identify PBS-1086 as a promising NFkB inhibitor to eliminate disease persistence and potentially prevent the emergence of resistance in patients.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65420
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Dataset Accession
Clustergrammer
Published October 2017
Web-based tool for visualizing and analyzing high-dimensional data as interactive and shareable heatmaps
4645
ARCHS4
Published September 2017
ARCHS4 provides access to gene counts from HiSeq 2000 and HiSeq 2500 platforms for human and mouse experiments from GEO ...
4645
Canned Analyses generated with the dataset
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Dataset Accession
Tool Name
Interactive heatmap visualization of RNA-seq dataset GSE65420
ARCHS4, Clustergrammer
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
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