Modelling Cancer in Drosophila

Abstract

Ever since the discovery of neoplastic and metastatic overgrowths in Drosophila melanogaster , the fly has been recognized as an excellent model organism for studying tumorigenesis. Recently, however, its relevance has become even more pronounced with the modelling of neoplasias in somatic clones of tissue using cooperative interactions between tumour suppressors and homologues of known mammalian oncogenes. The realization that many Drosophila neoplasias can be understood with respect to aberrant differentiation of stem cell progeny, together with the growing trend to postulate a stem cell origin of mammalian cancers, further highlight the enormous potential of fly cancer models to greatly increase our understanding of how human cancers develop.

A Genetic Analysis of Tumor Progression in Drosophila Identifies the Cohesin Complex as a Suppressor of Individual and Collective Cell Invasion

“…Although multilayered, amorphous, and invasive overgrowth is observed in lgl, scribble, or dlg mutant tissue, overgrowth is not observed when small mutant clones are generated, surrounded by WT tissue; here clones are restrained from overgrowth via a process known as ''cell competition.'' Mutant cells, despite undergoing excessive cell proliferation, are eliminated from the epithelium by Jun N-terminal kinase (JNK) pathway-mediated apoptosis (Brumby and Richardson, 2003;Nagata and Igaki, 2018). Both scribble and lgl 4 mutants have previously been shown to cooperate with oncogenic Notch overexpression to overcome the effects of cell competition and cause neoplastic overgrowths within the proliferative epithelial primordia known as the imaginal discs (Brumby and Richardson, 2003;Khan et al, 2013).…”

“…Mutant cells, despite undergoing excessive cell proliferation, are eliminated from the epithelium by Jun N-terminal kinase (JNK) pathway-mediated apoptosis (Brumby and Richardson, 2003;Nagata and Igaki, 2018). Both scribble and lgl 4 mutants have previously been shown to cooperate with oncogenic Notch overexpression to overcome the effects of cell competition and cause neoplastic overgrowths within the proliferative epithelial primordia known as the imaginal discs (Brumby and Richardson, 2003;Khan et al, 2013). We wanted to see whether we could observe a similar cooperative effect within the pupal notum, which at the developmental stage of our analysis (20-24 h APF), is largely post-mitotic.…”

Genetically Variant Human Pluripotent Stem Cells Selectively Eliminate Wild-Type Counterparts Through YAP-Mediated Cell Competition

“…The elimination of wild-type hPSCs which occurred in co-culture with variants is reminiscent of cell competition described in many different systems, whereby ''weaker,'' loser cells are eliminated in the presence of ''fitter'' winner cells (Bowling et al, 2019). Cell competition typically involves inducing either senescence (Bondar and Medzhitov, 2010) or apoptosis (Brumby and Richardson, 2003;Moreno et al, 2002;Sancho et al, 2013) in loser cells. From our time-lapse analysis of wild-type-RFP cells co-cultured with either variant-GFP cells or unlabeled wild-type cells as a control, it was evident that the loser cells were not arresting in co-cultures (Figure S3).…”