ArticleMolecular systems biology2012
Reverse engineering a hierarchical regulatory network downstream of oncogenic KRAS.
Article in Molecular systems biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
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- Vitamin D and Systems Biology.Nutrients · 2022Review
- Development of Metabolic Synthetic Lethality and Its Implications for Thyroid Cancer.Endocrinology and metabolism (Seoul, Korea) · 2022Article
- Role of the Transcription Factor FOSL1 in Organ Development and Tumorigenesis.International journal of molecular sciences · 2022Review
- An R package for generic modular response analysis and its application to estrogen and retinoic acid receptor crosstalk.Scientific reports · 2021Article
- FRA1 contributes to MEK-ERK pathway-dependent PD-L1 upregulation by KRAS mutation in premalignant human bronchial epithelial cells.American journal of translational research · 2020Article
- [RAS mutations at the molecular tumor conference].Der Pathologe · 2019Review
- Connecting signaling and metabolic pathways in EGF receptor-mediated oncogenesis of glioblastoma.PLoS computational biology · 2019Article
- Cell type-dependent differential activation of ERK by oncogenic KRAS in colon cancer and intestinal epithelium.Nature communications · 2019Article
- Mapping connections in signaling networks with ambiguous modularity.NPJ systems biology and applications · 2019Article
- Impact of measurement noise, experimental design, and estimation methods on Modular Response Analysis based network reconstruction.Scientific reports · 2018Article
- Reconstructing phosphorylation signalling networks from quantitative phosphoproteomic data.Essays in biochemistry · 2018Review
- REFINING CELLULAR PATHWAY MODELS USING AN ENSEMBLE OF HETEROGENEOUS DATA SOURCES.The annals of applied statistics · 2018Article
- Comparative Network Reconstruction using mixed integer programming.Bioinformatics (Oxford, England) · 2018Article
- Inferring Intracellular Signal Transduction Circuitry from Molecular Perturbation Experiments.Bulletin of mathematical biology · 2018Article
- A blueprint for human whole-cell modeling.Current opinion in systems biology · 2018Article
- inFRank: a ranking-based identification of influential genes in biological networks.Oncotarget · 2017Article
- An immediate-late gene expression module decodes ERK signal duration.Molecular systems biology · 2017Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RAS mutations are highly relevant for progression and therapy response of human tumours, but the genetic network that ultimately executes the oncogenic effects is poorly understood. Here, we used a reverse-engineering approach in an ovarian cancer model to reconstruct KRAS oncogene-dependent cytoplasmic and transcriptional networks from perturbation experiments based on gene silencing and pathway inhibitor treatments. We measured mRNA and protein levels in manipulated cells by microarray, RT-PCR and western blot analysis, respectively. The reconstructed model revealed complex interactions among the transcriptional and cytoplasmic components, some of which were confirmed by double pertubation experiments. Interestingly, the transcription factors decomposed into two hierarchically arranged groups. To validate the model predictions, we analysed growth parameters and transcriptional deregulation in the KRAS-transformed epithelial cells. As predicted by the model, we found two functional groups among the selected transcription factors. The experiments thus confirmed the predicted hierarchical transcription factor regulation and showed that the hierarchy manifests itself in downstream gene expression patterns and phenotype.
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