CECAD Microsite

Drosophila Tumor Model

Our interest has been focused on elucidating the complex role of the stress-inducible Jun-N-terminal kinase (JNK) pathway during malignant transformation using the Drosophila tumor model. By combining loss- and gain-of-function oncogenic events in visibly marked clonal tumors introduced into otherwise wild-type imaginal epithelium, we showed that the contribution of JNK signaling to tumor formation varied depending on the genotype of the tumor and also on the strength of the JNK signal (Uhlirova et al. 2005, PNAS). We further demonstrated the requirement of a matrix metalloproteinase (MMP) downstream of JNK for the spreading of highly malignant tumors to secondary sites (Uhlirova and Bohmann 2006, EMBO J).

Recently, we identified the actin-crosslinker Filamin/Cheerio (Cher) as a novel mediator of JNK-dependent malignancy (Külshammer and Uhlirova 2013, J Cell Sci). We showed that Cher up-regulation in invasive (rasV12, scrib1) tumors promotes tumor growth and invasiveness through interaction with the myosin II (MyoII) heavy chain subunit. In addition, Cher deregulates Hippo/Yki signaling, suggesting a possible link between Cher-dependent mechanical tension and attenuation of Hippo signaling in the tumor context