|
| Status |
Public on Feb 03, 2015 |
| Title |
Genetic and drug perturbation of components in the NFkB signaling pathway in 11-18 cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Through 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.
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| |
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| Overall design |
RNAseq analysis of 11-18 (EGFR-mutant lung adenocarcinoma) cells in the context of drug treatment with erlotinib and/or genetic or pharmacological inactivation of NFkB
|
| |
|
| Citation(s) |
25843712 |
| Submission date |
Jan 29, 2015 |
| Last update date |
Apr 11, 2022 |
| Contact name |
Saurabh Asthana |
| E-mail(s) |
saurabh.asthana@ucsf.edu
|
| Organization name |
UCSF
|
| Department |
Helen Diller Family Comprehensive Cancer Center
|
| Lab |
Olshen
|
| Street address |
1450 Third Street, Room HD276
|
| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (29)
|
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| Relations |
| BioProject |
PRJNA273960 |
| SRA |
SRP052950 |
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