Unscheduled expression of embryonic genes can lead to tumor formation

Tumor initiation is often linked to a loss of cellular identity. While key instructive genes are crucial during embryogenesis, many of these are then silenced during later developmental stages and in adulthood. Polycomb group proteins are among the main epigenetic silencing complexes and ensure appropriate silencing of many developmental genes in many cell types. In this work, Joana Torres, Jorge Beira and other collaborators at ETHZürich and Univ. Basel (Switzerland)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. Overall, it also shows the importance of maintaining the OFF state for many embryonic genes after their function has been fulfilled. Read more about how genes that have key functions in the embryo can start to drive tumor formation at later stages, if they are not correctly turned off, in the published eLIFE paper entitled "switch in transcription and cell fate governs the onset of an epigenetically-deregulated tumor in Drosophila".