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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| Format: | Article |
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eLife Sciences Publications Ltd
2018-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/32697 |
| _version_ | 1811201660786049024 |
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| author | Joana Torres Remo Monti Ariane L Moore Makiko Seimiya Yanrui Jiang Niko Beerenwinkel Christian Beisel Jorge V Beira Renato Paro |
| author_facet | Joana Torres Remo Monti Ariane L Moore Makiko Seimiya Yanrui Jiang Niko Beerenwinkel Christian Beisel Jorge V Beira Renato Paro |
| author_sort | Joana Torres |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T02:25:56Z |
| format | Article |
| id | doaj.art-9692943910b3480fa986d0ed4f215a01 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:25:56Z |
| publishDate | 2018-03-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-9692943910b3480fa986d0ed4f215a012022-12-22T03:52:01ZengeLife Sciences Publications LtdeLife2050-084X2018-03-01710.7554/eLife.32697A switch in transcription and cell fate governs the onset of an epigenetically-deregulated tumor in DrosophilaJoana Torres0https://orcid.org/0000-0002-5651-4575Remo Monti1Ariane L Moore2Makiko Seimiya3Yanrui Jiang4Niko Beerenwinkel5https://orcid.org/0000-0002-0573-6119Christian Beisel6Jorge V Beira7https://orcid.org/0000-0002-2884-4964Renato Paro8https://orcid.org/0000-0003-3308-2965Department of Biosystems Science and Engineering, ETH Zürich, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland; Swiss Institute of Bioinformatics, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland; Swiss Institute of Bioinformatics, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland; Faculty of Science, University of Basel, Basel, SwitzerlandTumor 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.https://elifesciences.org/articles/32697dedifferentiationembryonic-TF signaturetranscription factorsepigenetic regulationtumor onsetcell fate loss |
| spellingShingle | Joana Torres Remo Monti Ariane L Moore Makiko Seimiya Yanrui Jiang Niko Beerenwinkel Christian Beisel Jorge V Beira Renato Paro A switch in transcription and cell fate governs the onset of an epigenetically-deregulated tumor in Drosophila eLife dedifferentiation embryonic-TF signature transcription factors epigenetic regulation tumor onset cell fate loss |
| 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 | dedifferentiation embryonic-TF signature transcription factors epigenetic regulation tumor onset cell fate loss |
| url | https://elifesciences.org/articles/32697 |
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