Systematic name M14985
Brief description Genes up-regulated in SKOC-3 cells (ovarian cancer) after YB-1 (YBX1) [GeneID=4904] knockdown by RNAi.
Full description or abstract Y-box-binding protein 1 (YB-1), which is a member of the DNA-binding protein family containing a cold-shock domain, has pleiotropic functions in response to various environmental stimuli. As we previously showed that YB-1 is a global marker of multidrug resistance in ovarian cancer and other tumor types. To identify YB-1-regulated genes in ovarian cancers, we investigated the expression profile of YB-1 small-interfering RNA (siRNA)-transfected ovarian cancer cells using a high-density oligonucleotide array. YB-1 knockdown by siRNA upregulated 344 genes, including MDR1, thymidylate synthetase, S100 calcium binding protein and cyclin B, and downregulated 534 genes, including CXCR4, N-myc downstream regulated gene 1, E-cadherin and phospholipase C. Exogenous serum addition stimulated YB-1 translocation from the cytoplasm to the nucleus, and treatment with Akt inhibitors as well as Akt siRNA and integrin-linked kinase (ILK) siRNA specifically blocked YB-1 nuclear localization. Inhibition of Akt activation downregulated CXCR4 and upregulated MDR1 (ABCB1) gene expression. Administration of Akt inhibitor resulted in decrease in nuclear YB-1-positive cancer cells in a xenograft animal model. Akt activation thus regulates the nuclear translocation of YB-1, affecting the expression of drug-resistance genes and other genes associated with the malignant characteristics in ovarian cancer cells. Therefore, the Akt pathway could be a novel target of disrupting the nuclear translocation of YB-1 that has important implications for further development of therapeutic strategy against ovarian cancers.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17072343   Authors: Basaki Y,Hosoi F,Oda Y,Fotovati A,Maruyama Y,Oie S,Ono M,Izumi H,Kohno K,Sakai K,Shimoyama T,Nishio K,Kuwano M
Exact source Table 1S
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(show 37 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform AFFY_HG_U133
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Version history 3.0: First introduced

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