Review Article

Modelling Cooperative Tumorigenesis in Drosophila

Figure 1

Cell competition mechanisms. The three main types of cell competition are shown. Mutant cells are in pink, wild-type cells are in blue, hemocytes are in grey, and the basement membrane (basal lamina) is in purple. (a) Classical cell competition: within an epithelium, cells with reduced levels of dMyc, ribosomal subunits mutants (minutes), Jak-Stat or Wg signalling, or high levels of Hippo signalling (losers) are eliminated by apoptosis, induced by the surrounding wild-type cells (winners). The loser cells express on their cell surface the Flower-Lose () isoform (red dots), which marks them for elimination when in contact with the surrounding wild-type cells that express the Flower-Ubi () isoform (green dots). Additionally, signalling via the Spätzle ligand and Toll-Like Receptors (TLRs) in the loser cells triggers cell death via upregulation of cell death inducers, Rpr or Hid. Cells with upregulated Hippo signalling (or yki mutants) exhibit decreased dMyc levels, but cells with decreased ribosomal function, Jak-Stat, or Wg signalling undergo dMyc-independent cell competition. (b) Supercompetition: cells with high levels of dMyc, Jak-Stat, increased Wg signalling, or decreased Hippo signalling show “supercompetitor” behaviour and induce apoptosis in neighbouring wild-type cells. This occurs via the Flower-code or via Spätzle-TLR signalling in the loser cells. (c) Cell polarity mutant cell competition: cell polarity-impaired mutant cells are recognized by their epithelial neighbours or hemocytes (grey) and the TNFR-JNK signalling ligand, Egr (TNF), which is secreted by the wild-type epithelial cells or hemocytes. Mutant cells are removed by JNK-dependent and caspase-dependent apoptosis. JNK activation in neighbouring wild-type cells together with PVR, ELMO, and Mbc signalling is required in the wild-type cells for the removal of the dying cells. Hemocytes play the predominant role in engulfment and removal of the dead cells. The interaction of PTP10D in the mutant cell with SAS in the wild-type cell is important for “loser” cell fate of the polarity-impaired mutant cell. The Slit-Robo-Ena signalling pathway plays an important role in basal extrusion of the mutant cell, where the hemocytes are localized.
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