Editors' ChoiceCancer

Getting Rid of Unwanted Neighbors

Science Signaling  22 Mar 2011:
Vol. 4, Issue 165, pp. ec82
DOI: 10.1126/scisignal.4165ec82

In Drosophila imaginal epithelia, cells bearing mutations in neoplastic tumor suppressor genes, such as scrib or dlg, undergo cell death in a manner dependent on JNK and the presence of surrounding wild-type cells. Ohsawa et al. investigated the signaling pathways and mechanisms that mediate the elimination of neoplastic cells by normal tissue. In eye antennal disc with induced scrib or dlg clones, JNK signaling was activated by Eiger (a cell-surface tumor necrosis factor ligand) in the mutant clones and in the surrounding wild-type cells. JNK activation in the surrounding cells was independent of that in the mutant clones. Elimination of Eiger from the entire imaginal tissue led to overgrowth of scrib clones. Eiger-JNK signaling triggered increases in the mRNA and protein abundance of PVR (the Drosophila ortholog of the PDGF and VEGF receptor) in the mutant clones and surrounding wild-type cells. Elimination of scrib clones was reduced by RNA interference–mediated down-regulation of PVR in surrounding cells and enhanced by overexpression of PVR in surrounding cells. Mutant cells were phagocytosed by surrounding wild-type cells, a process that required the Ced-12 homolog ELMO (engulfment and cell motility) and the Ced-5 and DOCK180 homolog Mbc (myoblast city), which collectively act as a guanine nucleotide exchange factor for the GTPase Rac. Thus, activation of the JNK signaling pathway in Drosophila epithelia promotes the engulfment of neoplastic cells by the surrounding wild-type cells.

S. Ohsawa, K. Sugimura, K. Takino, T. Xu, A. Miyawaki, T. Igaki, Elimination of oncogenic neighbors by JNK-mediated engulfment in Drosophila. Dev. Cell 20, 315–328 (2011). [PubMed]