期刊
NATURE
卷 463, 期 7279, 页码 318-U68出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature08712
关键词
-
资金
- National Institute of Health [R01CA109755, R01CA101644, R01CA085628, R01NS061776]
- NCI Grand Opportunities TDDN Network [1RC2CA148308-01]
- In Silico Research Centre of Excellence [NCI-caBIG 29XS192]
- National Centers for Biomedical Computing NIH Roadmap Initiative [U54CA121852]
- National Institute of General Medical Sciences [P20GM075059]
- Italian Ministry of Welfare/Provincia di Benevento
- Fondation de Recherche Medicale
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/EBP beta and STAT3) emerge as synergistic initiators and master regulators of mesenchymal transformation. Ectopic co-expression of C/EBP beta 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/EBP beta 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据