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


ABSTRACT: 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.

SUBMITTER: Torres J 

PROVIDER: S-EPMC5862528 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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A switch in transcription and cell fate governs the onset of an epigenetically-deregulated tumor in <i>Drosophila</i>.

Torres Joana J   Monti Remo R   Moore Ariane L AL   Seimiya Makiko M   Jiang Yanrui Y   Beerenwinkel Niko N   Beisel Christian C   Beira Jorge V JV   Paro Renato R  

eLife 20180321


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 <i>Drosophila</i> epigenetic regulator, <i>polyhomeotic (ph).</i  ...[more]

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