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GENETIC AND GENOMIC STUDY OF CELL COMPETITION IN DROSOPHILA (Supercompetitors)
Start date: 01 Sep 2008, End date: 31 Aug 2013 PROJECT  FINISHED 

During initial stages a cell accumulating tumor-promoting mutations is usually surrounded by normal cells. Current cancer models do not incorporate this transition from a single cell to a field of cells, although it is probably critical, since the behavior of an individual tumor cell within the cell community has to be dictated by the hard-wired genetic program that controls its aberrant cell biology and modulated by the plastic interactions with neighboring normal cells. Study of model organisms, such as yeast, C. elegans, or Drosophila, has historically pioneered crucial contributions to processes with important implications in neoplasia. Recent work in Drosophila has proposed a role for cell-competition and super-competition in early stages of cancer formation. Cell competition is a type of cell-cell interaction in which more competitive cells replace less competitive cells (Morata and Ripoll, 1975; Moreno et al. 2002). During the last year, my laboratory has performed the first microarrays to find genes involved in cell competition, as well as developed an in vitro system for cell competition. The genes identified in the microarrays are not downstream dMyc but are rather induced at the boundaries where cell competition takes place and seem to be upstream apoptosis induction. The new genes will be studied in vivo in Drosophila and in vitro with RNAi. We will also perform other microarray settings to subdivide the genes in different categories. Thanks to the complete genome sequences of both Drosophila and humans, those genes could be used to find human homologues that could serve as novel markers and targets for the detection and/or treatment of cancer at earlier stages. The possible use of cell competition as a tool for cell replacement will also be pursued. We expect to patent at least two or three of the novel uncharacterized genes with human homologs.
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