Human Gene Set: WONG_PROTEASOME_GENE_MODULE


Standard name WONG_PROTEASOME_GENE_MODULE
Systematic name M11458
Brief description Genes that comprise the proteasome gene module
Full description or abstract A major goal of cancer research is to match specific therapies to molecular targets in cancer. Genome-scale expression profiling has identified new subtypes of cancer based on consistent patterns of variation in gene expression, leading to improved prognostic predictions. However, how these new genetic subtypes of cancers should be treated is unknown. Here, we show that a gene module map can guide the prospective identification of targeted therapies for genetic subtypes of cancer. By visualizing genome-scale gene expression in cancer as combinations of activated and deactivated functional modules, gene module maps can reveal specific functional pathways associated with each subtype that might be susceptible to targeted therapies. We show that in human breast cancers, activation of a poor-prognosis wound signature is strongly associated with induction of both a mitochondria gene module and a proteasome gene module. We found that 3-bromopyruvic acid, which inhibits glycolysis, selectively killed breast cells expressing the mitochondria and wound signatures. In addition, inhibition of proteasome activity by bortezomib, a drug approved for human use in multiple myeloma, abrogated wound signature expression and selectively killed breast cells expressing the wound signature. Thus, gene module maps may enable rapid translation of complex genomic signatures in human disease to targeted therapeutic strategies.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18199530   Authors: Wong DJ,Nuyten DS,Regev A,Lin M,Adler AS,Segal E,van de Vijver MJ,Chang HY
Exact source Table 3S
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Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
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identifier namespace		 HUMAN_GENE_SYMBOL
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Version history 3.0: First introduced

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