TY - JOUR TI - A switch in transcription and cell fate governs the onset of an epigenetically-deregulated tumor in Drosophila AU - Torres, Joana AU - Monti, Remo AU - Moore, Ariane L AU - Seimiya, Makiko AU - Jiang, Yanrui AU - Beerenwinkel, Niko AU - Beisel, Christian AU - Beira, Jorge V AU - Paro, Renato A2 - VijayRaghavan, K VL - 7 PY - 2018 DA - 2018/03/21 SP - e32697 C1 - eLife 2018;7:e32697 DO - 10.7554/eLife.32697 UR - https://doi.org/10.7554/eLife.32697 AB - 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. KW - dedifferentiation KW - embryonic-TF signature KW - transcription factors KW - epigenetic regulation KW - tumor onset KW - cell fate loss JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -