Spz/Toll-6 signal guides organotropic metastasis in Drosophila [RESEARCH ARTICLE]

ABSTRACT
Targeted cell migration plays important roles in developmental biology and disease processes, including in 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, invading receptive organs but not wing disc. Toll receptors are known to affect innate immunity and the tumor inflammatory microenvironment by modulating the NF-B pathway. Our RNA interference (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 [Spätzle (Spz) family molecules], and ectopic Spz expression renders the 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 Spz as a new pair of guidance molecules mediating organ-specific metastatic behavior and highlight a novel signaling mechanism for Toll-family receptors.

Source: DMM Disease Models and Mechanisms - October 6, 2019 Category: Biomedical Science Authors: Mishra-Gorur, K., Li, D., Ma, X., Yarman, Y., Xue, L., Xu, T. Tags: Drosophila as a Disease Model RESEARCH ARTICLE Source Type: research