Tumorigenesis and cell competition in <i>Drosophila</i> in the absence of <i>polyhomeotic</i> function.

Abstract

Cell competition is a homeostatic process that eliminates by apoptosis unfit or undesirable cells from animal tissues, including tumor cells that appear during the life of the organism. In <i>Drosophila</i> there is evidence that many types of oncogenic cells are eliminated by cell competition. One exception is cells mutant for <i>polyhomeotic</i> (<i>ph</i>), a member of the Polycomb family of genes; most of the isolated mutant <i>ph</i> clones survive and develop tumorous overgrowths in imaginal discs. To characterize the tumorigenic effect of the lack of <i>ph</i>, we first studied the growth of different regions of the wing disc deficient in <i>ph</i> activity and found that the effect is restricted to the proximal appendage. Moreover, we found that <i>ph</i>-deficient tissue is partially refractory to apoptosis. Second, we analyzed the behavior of clones lacking <i>ph</i> function and found that many suffer cell competition but are not completely eliminated. Unexpectedly, we found that nonmutant cells also undergo cell competition when surrounded by <i>ph-</i>deficient cells, indicating that within the same tissue cell competition may operate in opposite directions. We suggest two reasons for the incompleteness of cell competition in <i>ph</i> mutant cells: 1) These cells are partially refractory to apoptosis, and 2) the loss of <i>ph</i> function alters the identity of imaginal cells and subsequently their cell affinities. It compromises the winner/loser interaction, a prerequisite for cell competition.