Gene Set: WHITEHURST_PACLITAXEL_SENSITIVITY

Standard name WHITEHURST_PACLITAXEL_SENSITIVITY
Systematic name M10597
Brief description Genes that reduced viability of NCI-H1155 cells (non-small-cell lung cancer, NSCLC) in the presence of otherwise sublethal concentrations of paclitaxel [PubChem=4666], based on RNAi synthetic lethal screen.
Full description or abstract Abundant evidence suggests that a unifying principle governing the molecular pathology of cancer is the co-dependent aberrant regulation of core machinery driving proliferation and suppressing apoptosis. Anomalous proteins engaged in support of this tumorigenic regulatory environment most probably represent optimal intervention targets in a heterogeneous population of cancer cells. The advent of RNA-mediated interference (RNAi)-based functional genomics provides the opportunity to derive unbiased comprehensive collections of validated gene targets supporting critical biological systems outside the framework of preconceived notions of mechanistic relationships. We have combined a high-throughput cell-based one-well/one-gene screening platform with a genome-wide synthetic library of chemically synthesized small interfering RNAs for systematic interrogation of the molecular underpinnings of cancer cell chemoresponsiveness. NCI-H1155, a human non-small-cell lung cancer line, was employed in a paclitaxel-dependent synthetic lethal screen designed to identify gene targets that specifically reduce cell viability in the presence of otherwise sublethal concentrations of paclitaxel. Using a stringent objective statistical algorithm to reduce false discovery rates below 5%, we isolated a panel of 87 genes that represent major focal points of the autonomous response of cancer cells to the abrogation of microtubule dynamics. Here we show that several of these targets sensitize lung cancer cells to paclitaxel concentrations 1,000-fold lower than otherwise required for a significant response, and we identify mechanistic relationships between cancer-associated aberrant gene expression programmes and the basic cellular machinery required for robust mitotic progression.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17429401   Authors: Whitehurst AW,Bodemann BO,Cardenas J,Ferguson D,Girard L,Peyton M,Minna JD,Michnoff C,Hao W,Roth MG,Xie XJ,White MA
Exact source Table 1
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Organism Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform HUMAN_GENE_SYMBOL
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Version history 3.0: First introduced

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