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| Status |
Public on Mar 20, 2018 |
| Title |
An epigenetically-deregulated tumor state reveals a new role for embryonic transcription factors as cancer drivers |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Tumor initiation is often linked to a loss of cellular identity. Transcriptional programs determining cellular identity are preserved by epigenetically-acting chromatin factors. Although such regulators are among the most frequently mutated genes in cancer, it is not well understood how an aberration of the epigenetic status contributes to tumor onset. In this work, we investigated the transcriptional signature of tumors caused by disruption of the Drosophila epigenetic regulator, polyhomeotic (ph). In larval tissue, ph mutant cells show a shift towards an embryonic-like signature. Using loss- and gain-of-function experiments, we uncovered the embryonic transcription factor knirps (kni) as a new cancer driver. The oncogenic potential of kni lies in its ability to activate JAK/STAT signaling and block differentiation. Conversely, tumor growth in ph mutant cells can be substantially reduced by overexpressing a differentiation factor. This demonstrates that epigenetically derailed tumor conditions can be reversed by induction of differentiation.
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| Overall design |
Transcriptome analysis of ph505-tumors in Drosophila. Mutant clones FRT19A, ph505 generated in eye-antennal imaginal discs.
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| Contributor(s) |
Torres J, Monti R, Beira JV, Hofmann AL, Seimiya M, Jiang Y, Beerenwinkel N, Beisel C, Paro R |
| Citation(s) |
29560857 |
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| Submission date |
Jul 14, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Renato Paro |
| Organization name |
ETH Zurich
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| Department |
D-BSSE
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| Street address |
Mattenstrasse 26
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| City |
Basel |
| ZIP/Postal code |
4058 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL19132 |
Illumina NextSeq 500 (Drosophila melanogaster) |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA394512 |
| SRA |
SRP111954 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE101463_Counttable_collapsed.txt.gz |
227.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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