SUMMARY
Aggressive neoplastic growth can be initiated by a limited number of genetic alterations, such as the well-established cooperation between loss of cell architecture and hyperactive signaling pathways. However, our understanding of how these different alterations interact and influence each other remains very incomplete. Using Drosophila paradigms of imaginal wing disc epithelial growth, we have monitored the changes in Notch pathway activity according to the polarity status of cells and show that epithelial polarity changes directly impact the transcriptional output of the Notch pathway. Importantly, we show that this Notch pathway redirection is not mediated by a redeployment of Su(H), the Notch dedicated transcription factor, but relies on the cooperation with a combination of oncogenic transcription factors. Our work highlights in particular the role of the PAR domain containing bZIP transcription factor and Notch direct target Pdp1 for neoplastic growth.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
major revisions: - investigation of the role of Notch direct targets associated with new specific Su(H) binding - new figures on the role of Act87E and Pdp1 - streamlining of the Supplemental material - removal of the part on Xrp1 (results and discussion) to rationalise the manuscript