Figure 8.

Model of oncogene cooperation in malignant ras^V12, scrib^−/− tumors. The functional readout of JNK activation is determined by the status of the cooperating Ras signaling pathway. Loss of the apical–basal polarity in clones of imaginal epithelium lacking scribble function causes elimination of mutant cells through JNK-dependent apoptosis, possibly involving the transcriptional activation of hid (X Luo, D Bohmann and H Jasper, unpublished observation). Simultaneously, JNK stimulates actin cytoskeleton rearrangements. A third effect of JNK is the destabilization of the tissue environment and the basement membrane by mmp1 activation. Other, yet to be identified downstream targets of JNK may contribute to the development of malignancy. Survival signals delivered by activation of Ras/Raf/ERK signaling in scribble clones counteract apoptosis, enabling other JNK effectors to promote cell mobilization and invasion to ectopic sites. Multiple JNK functions require the Fos transcription factor.