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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 04, 2009 |
| Title |
Profiling of immortalized human lung epithelial cells following oncogenic KRAS expression and TBK1 suppression |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The purpose of the dataset is to analyze expression of genes induced by KRAS and regulated by TBK1
The proto-oncogene KRAS is mutated in a wide array of human cancers, most of which are aggressive and respond poorly to standard therapies. Although the identification of specific oncogenes has led to the development of clinically effective, molecularly targeted therapies in some cases, KRAS has remained refractory to this approach. An alternative strategy for targeting KRAS is to identify gene products that, when suppressed or inhibited, result in cell death only in the presence of an oncogenic allele. Here we have used systematic RNA interference (RNAi) to detect synthetic lethal partners of oncogenic KRAS and found that the non-canonical IkB kinase, TBK1, was selectively essential in cells that harbor mutant KRAS. Suppression of TBK1 induced apoptosis specifically in human cancer cell lines that depend on oncogenic KRAS expression. In these cells, TBK1 activated NF- B anti-apoptotic signals involving cREL and BCL-XL that were essential for survival, providing mechanistic insights into this synthetic lethal interaction. These observations identify TBK1 as a potential therapeutic target in KRAS mutant tumors and establish a general approach for the rational identification of co-dependent pathways in cancer.
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| Overall design |
Knock out of TBK1 in the contect of KRAS activation (mutant) and control (WT)
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| Contributor(s) |
Barbie D, Tamayo P |
| Citation(s) |
19847166 |
| Submission date |
Aug 14, 2009 |
| Last update date |
Dec 06, 2018 |
| Contact name |
Pablo Tamayo |
| E-mail(s) |
ptamayo@ucsd.edu
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| Phone |
508-259-0630
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| Organization name |
UCSD
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| Department |
Moores Cancer Center
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| Street address |
3855 Health Sciences Drive MC 0658
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
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| Platforms (1) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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| Samples (18)
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| GSM440259 |
AALE-KRAS + shTBK1, biological rep1 |
| GSM440260 |
AALE-KRAS + shTBK1, biological rep2 |
| GSM440261 |
AALE-KRAS + shTBK1, biological rep3 |
| GSM440262 |
AALE-KRAS + shGFP, biological rep1 |
| GSM440263 |
AALE-KRAS + shGFP, biological rep2 |
| GSM440264 |
AALE-KRAS + shGFP, biological rep3 |
| GSM440265 |
AALE-KRAS uninfected, biological rep1 |
| GSM440266 |
AALE-KRAS uninfected, biological rep2 |
| GSM440267 |
AALE-KRAS uninfected, biological rep3 |
| GSM440268 |
AALE-Vector + shTBK1, biological rep1 |
| GSM440269 |
AALE-Vector + shTBK1, biological rep2 |
| GSM440270 |
AALE-Vector + shTBK1, biological rep3 |
| GSM440271 |
AALE-Vector + shGFP, biological rep1 |
| GSM440272 |
AALE-Vector + shGFP, biological rep2 |
| GSM440273 |
AALE-Vector + shGFP, biological rep3 |
| GSM440274 |
AALE-Vector uninfected, biological rep1 |
| GSM440275 |
AALE-Vector uninfected, biological rep2 |
| GSM440276 |
AALE-Vector uninfected, biological rep3 |
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| This SubSeries is part of SuperSeries: |
| GSE17672 |
Profiling genes induced by oncogenic KRAS (G12V) and genes regulated by TBK1, a synthetic lethal partner of KRAS |
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| Relations |
| BioProject |
PRJNA123371 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE17643_RAW.tar |
39.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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