RRC ID 54161
Author Fernández-Espartero CH, Rizzo A, Fulford AD, Falo-Sanjuan J, Goutte-Gattat D, Ribeiro PS.
Title Prp8 regulates oncogene-induced hyperplastic growth in Drosophila.
Journal Development
Abstract 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 that is 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. The depletion of prp8 efficiently blocked Ras-, EGFR- and Notch-driven tumours but, in contrast, enhanced tumours that were 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.
Volume 145(22)
Published 2018-11-12
DOI 10.1242/dev.162156
PII dev.162156
PMID 30333215
PMC PMC6262796
MeSH Actins / metabolism Animals Carcinogenesis Cell Death Cell Differentiation Cell Polarity Cell Proliferation Drosophila Proteins / metabolism* Drosophila melanogaster / metabolism* Eye / growth & development Eye / metabolism Gastrointestinal Tract / metabolism Gastrointestinal Tract / pathology Gene Knockdown Techniques Hyperplasia Neoplasm Invasiveness Neoplasms / metabolism Neoplasms / pathology Oncogenes* Organ Specificity Phenotype RNA Interference RNA Splicing Factors / metabolism* ras Proteins / metabolism
IF 5.763
Times Cited 1
Resource
Drosophila 12082R-2 12082R-1 14619R-1 14619R-2 14619R-3 2904R-1 7288R-1 8232R-1 1950R-1 2224R-1 2224R-3 14884R-1 14884R-3 8877R-2 8877R-3 4673R-2 4673R-3 7857R-2 12359R-2 12359R-4 8493R-2 10889R-2 10889R-3