The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
RAS oncogene-mediated deregulation of the transcriptome: From molecular signature to function
Abstract
Transcriptome analysis of cancer cells has developed into a standard procedure to elucidate multiple features of the malignant process and to link gene expression to clinical properties. Gene expression profiling based on microarrays provides essentially correlative information and needs to be transferred to the functional level in order to understand the activity and contribution of individual genes or sets of genes as elements of the gene signature. To date, there exist significant gaps in the functional understanding of gene expression profiles. Moreover, the processes that drive the profound transcriptional alterations that characterize cancer cells remain mainly elusive. We have used pathway-restricted gene expression profiles derived from RAS oncogene-transformed cells and from RAS-expressing cancer cells to identify regulators downstream of the MAPK pathway.We describe the role of epigenetic regulation exemplified by the control of several immune genes in generic cell lines and colorectal cancer cells, particularly the functional interaction between signaling and DNA methylation. Moreover, we assess the role of the architectural transcription factor high mobility AT-hook 2 (HMGA2) as a regulator of the RAS-responsive transcriptome in ovarian epithelial cells. Finally, we describe an integrated approach combining pathway interference in colorectal cancer cells, gene expression profiling and computational analysis of regulatory elements of deregulated target genes. This strategy resulted in the identification of Y-box binding protein 1 (YBX1) as a regulator of MAPK-dependent proliferation and gene expression. The implications for a therapeutic application of HMGA2 gene silencing and the role of YBX1 as a prognostic factor are discussed.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Activation of RAS signaling leads to multiple intracellular changes including deregulation of transcriptional programs.
“Activation of the RAS signaling pathway leads to multiple intracellular changes, including the deregulation of transcriptional programs.3”
From USP22 deficiency leads to myeloid leukemia upon oncogenic Kras activation through a PU.1-dependent mechanism (2018) · cites this paper as [3]
Citations
Cites
Prevalence of ras gene mutations in human colorectal cancers
Bos, J. L., Fearon, E. R., Hamilton, S. R., Vries, M. V., BOOM, J. H. V., van der Eb, A. J., & Vogelstein, B. (1987) · Nature · doi:10.1038/327293a0 · Cited by 1,860
DNMT1 and DNMT3b cooperate to silence genes in human cancer cells
Rhee, I., Bachman, K. E., Park, B. H., Jair, K.-W., Yen, R.-W. C., Schuebel, K. E., Cui, H., Feinberg, A. P., Lengauer, C., Kinzler, K. W., et al. (2002) · Nature · doi:10.1038/416552a · Cited by 1,039
A novel role for high-mobility group A proteins in cellular senescence and heterochromatin formation
Narita, M., Narita, M., Krizhanovsky, V., Nuñez, S., Chicas, A., Hearn, S. A., Myers, M. P., & Lowe, S. W. (2006) · Cell · doi:10.1016/j.cell.2006.05.052 · Cited by 629
Molecular biology of HMGA proteins: hubs of nuclear function
Reeves, R. (2001) · Gene · doi:10.1016/s0378-1119(01)00689-8 · Cited by 541
CpG methylation is maintained in human cancer cells lacking DNMT1
Rhee, I. P., Jair, K., Yen, R.-W. C., Christoph Lengauer, C., Herman, J. G., Kinzler, K. W., Vogelstein, B., Baylin, S. B., & Schuebel, K. E. (2000) · Nature · doi:10.1038/35010000 · Cited by 453
Armeanu, S., Bitzer, M., Lauer, U. M., Venturelli, S., Pathil, A., Krusch, M., Kaiser, S., Jobst, J., Smirnow, I., Wagner, A., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4252 · Cited by 362
A genome-wide survey of RAS transformation targets
Zuber, J. A., Tchernitsa, O. I., Hinzmann, B., Schmitz, A.-C., Grips, M., Hellriegel, M., Sers, C., Rosenthal, A., & Schäfer, R. (2000) · Nature Genetics · doi:10.1038/72799 · Cited by 294
Self-citationAn elaborate pathway required for Ras-mediated epigenetic silencing
Gazin, C., Wajapeyee, N., Gobeil, S., Virbasius, C.-M. A., & Green, M. R. (2007) · Nature · doi:10.1038/nature06251 · Cited by 279
Analysis of the transcriptional program induced by Raf in epithelial cellsPreprint
Schulze, A., Lehmann, K. E., Jefferies, H. B. J., McMahon, M., & Downward, J. (2001) · Genes & Development · doi:10.1101/gad.191101 · Cited by 260
Immediate-Early and Delayed Primary Response Genes Are Distinct in Function and Genomic Architecture
Tullai, J. W., Schäffer, M., Mullenbrock, S., Sholder, G., Kasif, S., & Cooper, G. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702044200 · Cited by 214
Fritzmann, J., Morkel, M., Besser, D., Budczies, J., Kosel, F., Brembeck, F. H., Stein, U., Fichtner, I., Schlag, P. M., & Birchmeier, W. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.03.041 · Cited by 128
HMGA2 gene is a promising target for ovarian cancer silencing therapy
Malek, A. V., Ev, B., Noske, A., Sers, C., Aigner, A. M., Schäfer, R., & Tchernitsa, O. I. (2008) · International Journal of Cancer · doi:10.1002/ijc.23491 · Cited by 119
Self-citationTullai, J. W., Schäffer, M., Mullenbrock, S., Kasif, S., & Cooper, G. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309260200 · Cited by 98
Knösel, T., Emde, A., Schlüns, K., Chen, Y., Jürchott, K., Krause, M., Dietel, M., & Petersen, I. (2005) · Neoplasia · doi:10.1593/neo.05178 · Cited by 96
Finkbeiner, M., Astanehe, A., To, K., et al. (2009) · Oncogene · doi:10.1038/onc.2008.485 · Cited by 95
Jürchott, K., Kuban, R., Krech, T., Blüthgen, N., Stein, U., Walther, W., Friese, C., Kiełbasa, S. M., Ungethüm, U., Lund, P., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001231 · Cited by 90
Self-citationSuppressor gene alterations in the colorectal adenoma-carcinoma sequence
Cho, K. R., & Vogelstein, B. (1992) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240501124 · Cited by 83
Transcriptional basis of KRAS oncogene-mediated cellular transformation in ovarian epithelial cells
Tchernitsa, O. I., Sers, C., Zuber, J. A., Hinzmann, B., Grips, M., Schramme, A., Lund, P., Schwendel, A., Rosenthal, A., & Schäfer, R. (2004) · Oncogene · doi:10.1038/sj.onc.1207585 · Cited by 80
Self-citationSers, C., Kuner, R., Falk, C. S., Lund, P., Sueltmann, H., Braun, M., Buneß, A., Ruschhaupt, M., Conrad, J., Mang‐Fatehi, S., et al. (2009) · International Journal of Cancer · doi:10.1002/ijc.24557 · Cited by 80
Self-citationOncogenic HRAS suppresses clusterin expression through promoter hypermethylation
Lund, P., Weißhaupt, K., Mikeska, T., Jammas, D., Chen, X. '., Kuban, R., Ungethüm, U., Krapfenbauer, U., Herzel, H.-P., Schäfer, R., et al. (2006) · Oncogene · doi:10.1038/sj.onc.1209502 · Cited by 68
Self-citationCui, T., & Leng, F. (2007) · Biochemistry · doi:10.1021/bi701269s · Cited by 64
Alterations in DNA methylation in human colon neoplasia
Feinberg, A. P., & Vogelstein, B. (1987) · Seminars in Surgical Oncology · doi:10.1002/ssu.2980030304 · Cited by 61
Biomarkers Downstream of RAS: A Search for Robust Transcriptional Targets
Győrffy, B., & Schäfer, R. (2010) · Current Cancer Drug Targets · doi:10.2174/156800910793357916 · Cited by 29
Self-citationGlobal Effects of Ras Signaling on the Genetic Program in Mammalian Cells
Schäfer, R., Tchernitsa, O. I., & Sers, C. (2006) · Springer eBooks · doi:10.1007/1-4020-4708-8_8 · Cited by 14
Self-citationEffects of Ras Signaling on Gene Expression Analyzed by Customized Microarrays
Tchernitsa, O. I., Sers, C., Geflitter, A., & Schäfer, R. (2006) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(05)07031-x · Cited by 9
Self-citationDer, C. J. (2006) · Springer eBooks · doi:10.1007/1-4020-4708-8 · Cited by 5
Flagged first, then by citations
Cited by
Sorted by citations
Melo-Cardenas, J., Xu, Y., Wei, J., Tan, C., Kong, S., Gao, B., Montauti, E., Kirsammer, G., Licht, J. D., Yu, J., et al. (2018) · Blood · doi:10.1182/blood-2017-10-811760 · Cited by 84
Metadata
- Authors
- Schäfer, R., & Sers, C.
- Affiliations
- Charité – Universitätsmedizin Berlin (DE)
- Corresponding author
- Schäfer, Reinhold
- Venue
- Advances in Enzyme Regulation
- Publisher
- Elsevier BV
- Published
- 2011
- Volume
- 51
- Issue
- 1
- Pages
- 126-136
- ISSN
- 0065-2571 (ISSN-L)
- OpenAlex
- W2039691472
- Cited by
- 12
- References
- 26
- Citations by year
- 2026: 1 · 2023: 1 · 2021: 1 · 2019: 1 · 2018: 1 · 2016: 1 · 2014: 1 · 2013: 1 · 2012: 3
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Advances in Enzyme Regulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Deutsche Krebshilfe
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- oncogenic Ras, transcriptome deregulation, MAPK signaling, gene expression signatures, epigenetic regulation, DNA methylation, immune-related genes, HMGA2, YB-1, colorectal cancer, ovarian epithelial cells, transcriptional regulation, gene silencing, prognostic factors, cell proliferation
- MeSH terms
- Animals, Humans, Genes, ras, Transcription Factors, Signal Transduction, ras Proteins, Gene Expression Profiling, Mitogen-Activated Protein Kinases, Microarray Analysis, Epigenomics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
