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| Status |
Public on Jun 10, 2016 |
| Title |
An ectopic network of transcription factors regulated by Hippo signaling drives growth and invasion of a malignant tumor model [larval imaginal discs] |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Cancer cells have abnormal gene expression profiles, however, the transcription factors and the architecture of the regulatory network that drive cancer specific gene expression is often not known. Here we studied a model of Ras-driven invasive tumorigenesis in Drosophila epithelial tissues and combined in vivo genetics with high-throughput sequencing and computational modeling to decipher the regulatory logic of tumor cells. Surprisingly, we discovered that the bulk of the tumor specific gene expression is driven by an ectopic network of a few transcription factors that are overexpressed and/or hyperactivated in tumor cells. These factors are Stat, AP-1, the bHLH proteins Myc and AP-4, the nuclear hormone receptor Ftz-f1, the nuclear receptor coactivator Taiman/AIB1, and Mef2. Notably, many of these transcription factors are also hyperactivated in human tumors. Bioinformatics analysis predicted that these factors directly regulate the majority of the tumor specific gene expression, that they are interconnected by extensive cross-regulation, and that they show a high degree of co-regulation of target genes. Indeed, the factors of this network were required in multiple epithelia for tumor growth and invasiveness and knock-down of individual factors caused a reversion of the tumor specific expression profile, but had no observable effect on normal tissues. We further found that the Hippo pathway effector Yki/Sd was strongly activated in tumor cells and initiated cellular reprogramming by activating several transcription factors of this network. Thus, modeling regulatory networks identified an ectopic yet highly ordered network of master regulators that control tumor cell specific gene expression.
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| Overall design |
RNA-seq gene expression profiling across Drosophila 3rd instar larval imaginal discs in a control and different genetic perturbations.
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| Contributor(s) |
Atkins M, Potier D, Romanelli L, Jacobs J, Mach J, Hamaratoglu F, Aerts S, Halder G |
| Citation(s) |
27476594 |
| Submission date |
Jul 26, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Delphine Potier |
| E-mail(s) |
potier@ciml.univ-mrs.fr
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| Organization name |
CIML
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| Street address |
163 avenue de luminy
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| City |
Marseille |
| ZIP/Postal code |
13009 |
| Country |
France |
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| Platforms (1) |
| GPL13304 |
Illumina HiSeq 2000 (Drosophila melanogaster) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE71354 |
An ectopic network of transcription factors regulated by Hippo signaling drives growth and invasion of a malignant tumor model |
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| Relations |
| BioProject |
PRJNA291028 |
| SRA |
SRP061606 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE71350_all_samples.countstable.txt.gz |
206.0 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
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