Although developmental signalling pathways control tumourigenic growth, the cellular mechanisms that abnormally proliferating cells rely on are still largely unknown. Drosophila melanogaster is a genetically tractable model used to study how specific genetic changes confer advantageous tumourigenic traits. Despite recent efforts, the role of deubiquitylating enzymes in cancer is particularly understudied. We performed a Drosophila in vivo RNAi screen to identify deubiquitylating enzymes that modulate RasV12-induced hyperplastic growth. We identified the spliceosome core component Prp8 as a crucial regulator of Ras-, EGFR-, Notch- or RET-driven hyperplasia. Loss of prp8 function alone decreased cell proliferation, increased cell death and affected cell differentiation and polarity. In hyperplasia, Prp8 supported tissue overgrowth independently of caspase-dependent cell death. prp8 depletion efficiently blocked Ras-, EGFR- and Notch-driven tumours but, in contrast, enhanced tumours driven by oncogenic RET, suggesting a context-specific role in hyperplasia. These data show, for the first time, that Prp8 regulates hyperplasia and extend recent observations on the potential role of the spliceosome in cancer. Our findings suggest that targeting Prp8 could be beneficial in specific tumour types.
Prp8 regulates oncogene-induced hyperplastic growth in Drosophila
These authors contributed equally to this work
Currently Viewing Accepted Manuscript - Newer Version Available
Cecilia H. Fernández-Espartero, Alberto Rizzo, Alexander D. Fulford, Julia Falo-Sanjuan, Damien Goutte-Gattat, Paulo S. Ribeiro; Prp8 regulates oncogene-induced hyperplastic growth in Drosophila. Development 2018; dev.162156. doi: https://doi.org/10.1242/dev.162156
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