dUev1a modulates TNF-JNK mediated tumor progression and cell death in Drosophila.

Loss of cell polarity cooperates with oncogenic Ras to induce JNK-dependent tumor growth and invasion. To identify additional genes that modulate tumor progression, we have performed a genetic screen in Drosophila and found that loss of dUev1a, the ortholog of mammalian Uev1, suppressed lgl(-/-)/Ras(V12) induced JNK-mediated tumor growth and invasion. Furthermore, loss of dUev1a suppressed TNF ortholog Eiger-induced JNK-mediated cell invasion and cell death. Finally, dUev1a cooperated with Bendless to activate JNK signaling through dTRAF2. Together, our data indicate that dUev1a encodes an essential component of the evolutionary conserved TNF-JNK signaling pathway that modulates tumor progression and cell death in metazoan.