Gene Set: KRAS.AMP.LUNG_UP.V1_UP

Standard name KRAS.AMP.LUNG_UP.V1_UP
Systematic name M2860
Brief description Genes up-regulated in epithelial lung cancer cell lines over-expressing KRAS [GeneID=3845] gene.
Full description or abstract Profiling of immortalized human lung epithelial cells following oncogenic KRAS expression and TBK1 suppression. 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-kappaB 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. Knock out of TBK1 in the contect of KRAS activation (mutant) and control (WT).
Collection C6: oncogenic signatures
Source publication Pubmed GSE17643   Authors: Boehm J
Exact source AALE-KRAS WT vs AALE-Vector: top 150 genes (diff. means)
Related gene sets (show 7 additional gene sets from the source publication)

(show 10 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Pablo Tamayo (Broad Institute)
Source platform HUMAN_GENE_SYMBOL
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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