Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7279
pubmed:dateCreated
2010-1-21
pubmed:databankReference
pubmed:abstractText
The inference of transcriptional networks that regulate transitions into physiological or pathological cellular states remains a central challenge in systems biology. A mesenchymal phenotype is the hallmark of tumour aggressiveness in human malignant glioma, but the regulatory programs responsible for implementing the associated molecular signature are largely unknown. Here we show that reverse-engineering and an unbiased interrogation of a glioma-specific regulatory network reveal the transcriptional module that activates expression of mesenchymal genes in malignant glioma. Two transcription factors (C/EBPbeta and STAT3) emerge as synergistic initiators and master regulators of mesenchymal transformation. Ectopic co-expression of C/EBPbeta and STAT3 reprograms neural stem cells along the aberrant mesenchymal lineage, whereas elimination of the two factors in glioma cells leads to collapse of the mesenchymal signature and reduces tumour aggressiveness. In human glioma, expression of C/EBPbeta and STAT3 correlates with mesenchymal differentiation and predicts poor clinical outcome. These results show that the activation of a small regulatory module is necessary and sufficient to initiate and maintain an aberrant phenotypic state in cancer cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
21
pubmed:volume
463
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
318-25
pubmed:dateRevised
2010-8-17
pubmed:meshHeading
pubmed-meshheading:20032975-Animals, pubmed-meshheading:20032975-Brain Neoplasms, pubmed-meshheading:20032975-CCAAT-Enhancer-Binding Protein-beta, pubmed-meshheading:20032975-Cell Differentiation, pubmed-meshheading:20032975-Cell Line, Tumor, pubmed-meshheading:20032975-Cell Transformation, Neoplastic, pubmed-meshheading:20032975-Computational Biology, pubmed-meshheading:20032975-Gene Expression Regulation, Neoplastic, pubmed-meshheading:20032975-Gene Regulatory Networks, pubmed-meshheading:20032975-Glioma, pubmed-meshheading:20032975-Humans, pubmed-meshheading:20032975-Mesenchymal Stem Cells, pubmed-meshheading:20032975-Mesoderm, pubmed-meshheading:20032975-Mice, pubmed-meshheading:20032975-Mice, Inbred NOD, pubmed-meshheading:20032975-Mice, SCID, pubmed-meshheading:20032975-Neoplasm Invasiveness, pubmed-meshheading:20032975-Neurons, pubmed-meshheading:20032975-Nuclear Reprogramming, pubmed-meshheading:20032975-Prognosis, pubmed-meshheading:20032975-Reproducibility of Results, pubmed-meshheading:20032975-STAT3 Transcription Factor, pubmed-meshheading:20032975-Transcription, Genetic
pubmed:year
2010
pubmed:articleTitle
The transcriptional network for mesenchymal transformation of brain tumours.
pubmed:affiliation
Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural