GenomeRNAi - a database for RNAi phenotypes and reagents
TitleScreen TitleAssayBiomodelSpecies
A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Luo et al. (2009) Synthetic lethal interaction with Ras Synthetic lethal interaction with RasDLD1 colon adenocarcinoma cells (Ras mutant and wildtype)H. sapiens

Abstract

Oncogenic mutations in the small GTPase Ras are highly prevalent in cancer, but an understanding of the vulnerabilities of these cancers is lacking. We undertook a genome-wide RNAi screen to identify synthetic lethal interactions with the KRAS oncogene. We discovered a diverse set of proteins whose depletion selectively impaired the viability of Ras mutant cells. Among these we observed a strong enrichment for genes with mitotic functions. We describe a pathway involving the mitotic kinase PLK1, the anaphase-promoting complex/cyclosome, and the proteasome that, when inhibited, results in prometaphase accumulation and the subsequent death of Ras mutant cells. Gene expression analysis indicates that reduced expression of genes in this pathway correlates with increased survival of patients bearing tumors with a Ras transcriptional signature. Our results suggest a previously underappreciated role for Ras in mitotic progression and demonstrate a pharmacologically tractable pathway for the potential treatment of cancers harboring Ras mutations.

Screen details


Stable Id: GR00018-A-0
Screen title: Synthetic lethal interaction with Ras
Assay: Synthetic lethal interaction with Ras
Method: Micoarray hybridization
Scope:
Screen type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: DLD1 colon adenocarcinoma cells (Ras mutant and wildtype)
Library: , shRNA-mir (G. Hannon)
Reagent type: shRNA
Score type: Log2 diff MUT-WT (and P-value)
Cutoff: -0.7 (0.3)
Notes: