Modelling Cooperative Tumorigenesis in Drosophila

Figure 4

Different modes of cooperative tumorigenesis. Examples of different modes of cooperative tumorigenesis. Mutant cells are in pink, Ras^V12-expressing cells are in green, wild-type cells are in blue, delaminated mutant cells are in dark pink, and the basement membrane (basal lamina) is in purple. (a) Intraclonal cooperation with cell polarity mutants and Ras^V12: JNK activation in the tumour cells cooperates with oncogenic Ras signalling to promote tumour overgrowth and invasion. (b) Interclonal cooperation with cell polarity mutants and Ras^V12: JNK signalling and Hippo pathway impairment in the scrib mutant cells lead to the production of Upd, which induces Dome-Jak-Stat signalling in the surrounding Ras^V12-expressing cells, thereby inducing their overgrowth and invasion. (c) Interclonal cooperation with a mitochondrial mutant overexpressing Ras^V12 and Ras^V12-expressing surrounding cells: Upd and Wg are produced by the mitochondrial mutant Ras^V12-expressing surrounding cells (see Figure 3(c)), which induce upregulation of Dome-Jak-Stat and Wg signalling, respectively, in the Ras^V12 cells to induce their neoplastic overgrowth and invasion. (d) Delaminating cells cooperation: in tumours generated by chromosome instability (CIN) mutants (rod, bub3,  and  asp) or mutants that effect spindle orientation (scrib, dlg, and mud), some cells delaminate, resulting in two populations of cells, which in the case of spindle orientation mutants are not genetically different. The delaminated cell population produces the Wg and Upd ligands to upregulate Wg and Dome-Jak-Stat pathways, respectively, in the nondelaminated cells, thereby inducing their proliferation.

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