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          Institute: MPI für molekulare Genetik     Collection: Department of Developmental Genetics     Display Documents

ID: 536203.0, MPI für molekulare Genetik / Department of Developmental Genetics
Identification of Y-box binding protein 1 as a core regulator of MEK/ERK pathway dependent gene signatures in colorectal cancer cells.
Authors:Jürchott, Karsten; Kuban, Ralf-Jürgen; Krech, Till; Blüthgen, Nils; Stein, Ulrike; Walther, Wolfgang; Friese, Christian; iełbasa, Szymon M.; Ungethüm, Ute; Lund, Per; Knösel, Thomas; Kemmner, Wolfgang; Morkel, Markus; Fritzmann, Johannes; Schlag, Peter M.; Birchmeier, Walter; Krueger, Tammo; Sperling, Silke; Sers, Christine; Royer, Hans-Dieter; Herzel, Hanspeter; Schäfer, Reinhold
Research Context:Our work was supported by the National Genome Research Network (NGFN1), ColoNet, IG Mutanom (systems biology programs, Federal Ministry of Education and Research), Deutsche Krebshilfe/Dr. Mildred Scheel-Stiftung (grant 10-2187-Scha-2), and Deutsche Forschungsgemeinschaft (SFB 618, TPA3, grant to HH and RS; JU 2738/1-1). The funders had no role in experimental design, data collection and analysis, decision to publish, or preparation of the manuscript.
Date of Publication (YYYY-MM-DD):2010-12-02
Title of Journal:PLoS Genetics
Journal Abbrev.:PLOS Genet.
Issue / Number:12
Start Page:e1001231
End Page:e1001231
Full name of Issue-Editor(s):Vivian G. Cheung, University of Pennsylvania, United States of America
Copyright:© 2010 Jürchott et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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
Version Comment:Automatic journal name synchronization
Communicated by:Bernhard G. Herrmann
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Laboratory of Molecular Tumor Pathology, Universitätsmedizin Berlin, Berlin, Germany;
2.Laboratory of Functional Genomics, Universitätsmedizin Berlin, Berlin, Germany;
3.Institute for Theoretical Biology, Humboldt University, Berlin, Germany;
4.Max Delbrück Center for Molecular Medicine, Berlin, Germany;
5.Institute of Pathology, Friedrich-Schiller-University Jena, Jena, Germany;
6.Charité Comprehensive Cancer Center, Berlin, Germany;
7.Center of Advanced European Studies and Research, Bonn, Germany;
9.Institute of Human Genetics and Anthropology, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
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