Modelling Cooperative Tumorigenesis in Drosophila

Figure 3

Non-cell-autonomous overgrowth. Examples of different types of non-cell-autonomous overgrowth. 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) Cell polarity or endocytosis mutant cells are induced by JNK signalling to undergo cell death and induce non-cell-autonomous overgrowth of the surrounding wild-type cells. In vps25 or tsg101 (ept) endocytic mutants, which also show apicobasal cell polarity defects, ectopic activation of Notch signalling leads to the expression and secretion of the Dome-Jak-Stat pathway ligand, Upd, which promotes non-cell-autonomous proliferation and overgrowth of surrounding tissue. In scrib mutant cells, elevated JNK signalling, and impaired Hippo signalling, leads to transcriptional upregulation of Upd, which activates Dom-Jak-Stat signalling in the surrounding wild-type cells, thereby inducing their proliferation. (b) Undead cells, where apoptosis is initiated, but effector caspase activity is blocked, emit morphogens (such as Wg, Dpp, and Hh) that promote proliferation of their wild-type epithelial neighbours, thereby leading to non-cell-autonomous overgrowth. (c) Mitochondrial mutants expressing Ras^V12 lead to non-cell-autonomous overgrowth. The mitochondrial impairment results in the production of ROS, which induces JNK activation, which, in turn, results in Hippo pathway impairment, leading to expression of the Yki targets, Upd and Wg. Upd elevates Jak/Stat signalling and Wg induces Wg pathway signalling in the surrounding wild-type cells to promote their overgrowth.

(a)

(b)

(c)