Spz/Toll-6 signal guides organotropic metastasis in Drosophila

Abstract

Targeted cell migration plays important roles in developmental biology and disease processes including metastasis. Drosophila tumors exhibit traits characteristic of human cancers, providing a powerful model to study developmental and cancer biology. We now find that cells derived from Drosophila eye disc tumors also display organ specific metastasis to invade receptive organs but not wing disc. Toll receptors are known to affect innate immunity and tumor inflammatory microenvironment by modulating the NF-κB pathway. Our RNAi screen and genetic analyses show that Toll-6 is required for migration and invasion of the tumor cells. Further, receptive organs express Toll-ligands, Spz family molecules, and ectopic Spz expression renders wing disc receptive to metastasis. Finally, Toll-6 promotes metastasis by activating JNK signaling, a key regulator of cell migration. Hence, we report Toll-6 and Spätzle as a new pair of guidance molecules mediating organ-specific metastasis behavior and highlight a novel signaling mechanism for Toll family receptors.