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

• DOI: 10.7554/elife.32697
• Publication Date: 2018-03-20T12:02:12Z
• Authors: Joana Torres; Remo Monti; Ariane L Moore; Makiko Seimiya; Yanrui Jiang; Niko Beerenwinkel; Christian Beisel; Jorge V Beira; Renato Paro
• Keywords: Cell fate determination

Tumor initiation is often linked to a loss of cellular identity. Transcriptional programs determining identity are preserved by epigenetically-acting chromatin factors. Although such regulators among the most frequently mutated genes in cancer, it not well understood how an abnormal epigenetic condition contributes tumor onset. In this work, we investigated gene signature tumors caused disruption Drosophila regulator, polyhomeotic (ph). larval tissue ph mutant cells show shift towards embryonic-like signature. Using loss- and gain-of-function experiments uncovered embryonic transcription factor knirps (kni) as new oncogene. The oncogenic potential kni lies its ability activate JAK/STAT signaling block differentiation. Conversely, growth can be substantially reduced overexpressing differentiation factor. This demonstrates that epigenetically derailed conditions reversed when targeting key players transcriptional network.