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A switch in transcription and cell fate governs the onset of an epigenetically-deregulated tumor in Drosophila

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 abnormal...

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Autores principales: Torres, Joana, Monti, Remo, Moore, Ariane L, Seimiya, Makiko, Jiang, Yanrui, Beerenwinkel, Niko, Beisel, Christian, Beira, Jorge V, Paro, Renato
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862528/
https://www.ncbi.nlm.nih.gov/pubmed/29560857
http://dx.doi.org/10.7554/eLife.32697
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author Torres, Joana
Monti, Remo
Moore, Ariane L
Seimiya, Makiko
Jiang, Yanrui
Beerenwinkel, Niko
Beisel, Christian
Beira, Jorge V
Paro, Renato
author_facet Torres, Joana
Monti, Remo
Moore, Ariane L
Seimiya, Makiko
Jiang, Yanrui
Beerenwinkel, Niko
Beisel, Christian
Beira, Jorge V
Paro, Renato
author_sort Torres, Joana
collection PubMed
description 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 abnormal epigenetic condition contributes to tumor onset. In this work, we investigated the gene 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 oncogene. 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 when targeting key players in the transcriptional network.
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spelling pubmed-58625282018-03-22 A switch in transcription and cell fate governs the onset of an epigenetically-deregulated tumor in Drosophila Torres, Joana Monti, Remo Moore, Ariane L Seimiya, Makiko Jiang, Yanrui Beerenwinkel, Niko Beisel, Christian Beira, Jorge V Paro, Renato eLife Developmental Biology 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 abnormal epigenetic condition contributes to tumor onset. In this work, we investigated the gene 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 oncogene. 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 when targeting key players in the transcriptional network. eLife Sciences Publications, Ltd 2018-03-21 /pmc/articles/PMC5862528/ /pubmed/29560857 http://dx.doi.org/10.7554/eLife.32697 Text en © 2018, Torres et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology
Torres, Joana
Monti, Remo
Moore, Ariane L
Seimiya, Makiko
Jiang, Yanrui
Beerenwinkel, Niko
Beisel, Christian
Beira, Jorge V
Paro, Renato
A switch in transcription and cell fate governs the onset of an epigenetically-deregulated tumor in Drosophila
title A switch in transcription and cell fate governs the onset of an epigenetically-deregulated tumor in Drosophila
title_full A switch in transcription and cell fate governs the onset of an epigenetically-deregulated tumor in Drosophila
title_fullStr A switch in transcription and cell fate governs the onset of an epigenetically-deregulated tumor in Drosophila
title_full_unstemmed A switch in transcription and cell fate governs the onset of an epigenetically-deregulated tumor in Drosophila
title_short A switch in transcription and cell fate governs the onset of an epigenetically-deregulated tumor in Drosophila
title_sort switch in transcription and cell fate governs the onset of an epigenetically-deregulated tumor in drosophila
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862528/
https://www.ncbi.nlm.nih.gov/pubmed/29560857
http://dx.doi.org/10.7554/eLife.32697
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