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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents



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ID: 556502.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
Identification of Y-box binding protein 1 as a core regulator of MEK/ERK pathway-dependent gene signatures in colorectal cancer cells
Authors:Jürchott, K.; Kuban, R. J.; Krech, T.; Blüthgen, N.; Stein, U.; Walther, W.; Friese, C.; Kielbasa, S. M.; Ungethüm, U.; Lund, P.; Knosel, T.; Kemmner, W.; Morkel, M.; Fritzmann, J.; Schlag, P. M.; Birchmeier, W.; Krueger, T.; Sperling, S.; Sers, C.; Royer, H. D.; Herzel, H.; Schäfer, R.
Language:English
Date of Publication (YYYY-MM-DD):2010-12-02
Title of Journal:PLoS Genetics
Volume:6
Issue / Number:12
Start Page:e1001231
End Page:e1001231
Copyright:© 2010 Jürchott et al
Review Status:not specified
Audience:Experts Only
Abstract / Description:Transcriptional signatures are an indispensible source of correlative information on disease-related molecular alterations on a genome-wide level. Numerous candidate genes involved in disease and in factors of predictive, as well as of prognostic, value have been deduced from such molecular portraits, e.g. in cancer. However, mechanistic insights into the regulatory principles governing global transcriptional changes are lagging behind extensive compilations of deregulated genes. To identify regulators of transcriptome alterations, we used an integrated approach combining transcriptional profiling of colorectal cancer cell lines treated with inhibitors targeting the receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase pathway, computational prediction of regulatory elements in promoters of co-regulated genes, chromatin-based and functional cellular assays. We identified commonly co-regulated, proliferation-associated target genes that respond to the MAPK pathway. We recognized E2F and NFY transcription factor binding sites as prevalent motifs in those pathway-responsive genes and confirmed the predicted regulatory role of Y-box binding protein 1 (YBX1) by reporter gene, gel shift, and chromatin immunoprecipitation assays. We also validated the MAPK-dependent gene signature in colorectal cancers and provided evidence for the association of YBX1 with poor prognosis in colorectal cancer patients. This suggests that MEK/ERK-dependent, YBX1-regulated target genes are involved in executing malignant properties.
Comment of the Author/Creator:E-mail: reinhold.schaefer@charite.de
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:Laboratory of Molecular Tumor Pathology, Universitätsmedizin Berlin, Berlin, Germany
Laboratory of Functional Genomics, Universitätsmedizin Berlin, Berlin, Germany
Institute for Theoretical Biology, Humboldt University, Berlin, Germany
Max Delbrück Center for Molecular Medicine, Berlin, Germany Institute of Pathology, Friedrich-Schiller-University Jena, Jena, Germany
Charité Comprehensive Cancer Center, Berlin, Germany
Center of Advanced European Studies and Research, Bonn, Germany
Institute of Human Genetics and Anthropology, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
Identifiers:ISSN:1553-7404 (Electronic) [ID No:1]
DOI:10.1371/journal.pgen.1001231 [ID No:2]
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