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  Identification of Y-box binding protein 1 as a core regulator of MEK/ERK pathway dependent gene signatures in colorectal cancer cells.

Jürchott, K., Kuban, R.-J., Krech, T., Blüthgen, N., Stein, U., Walther, W., et al. (2010). Identification of Y-box binding protein 1 as a core regulator of MEK/ERK pathway dependent gene signatures in colorectal cancer cells. PLoS Genetics, 6(12), e1001231-e1001231. doi:doi:10.1371/journal.pgen.1001231.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-79D3-C Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-79D5-8
Genre: Journal Article
Alternative Title : PLOS Genet.

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 Creators:
Jürchott, Karsten, Author
Kuban, Ralf-Jürgen, Author
Krech, Till, Author
Blüthgen, Nils, Author
Stein, Ulrike, Author
Walther, Wolfgang, Author
Friese, Christian, Author
iełbasa, Szymon M., Author
Ungethüm, Ute, Author
Lund, Per, Author
Knösel, Thomas, Author
Kemmner, Wolfgang, Author
Morkel, Markus1, Author              
Fritzmann, Johannes, Author
Schlag, Peter M., Author
Birchmeier, Walter, Author
Krueger, Tammo, Author
Sperling, Silke2, Author              
Sers, Christine, Author
Royer, Hans-Dieter, Author
Herzel, Hanspeter, AuthorSchäfer, Reinhold, Author more..
Affiliations:
1Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, escidoc:1433548              
2Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, escidoc:1433550              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2010-12-02
 Publication Status: Published in print
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 Identifiers: eDoc: 536203
DOI: doi:10.1371/journal.pgen.1001231
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Title: PLoS Genetics
  Alternative Title : PLOS Genet.
Source Genre: Journal
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Pages: - Volume / Issue: 6 (12) Sequence Number: - Start / End Page: e1001231 - e1001231 Identifier: ISSN: 1553-7390