Abstract
ABSTRACTTargeted 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-κB 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.
Highlights
Targeted cell migration and invasion play important roles in a variety of biological and disease processes
To further utilize Drosophila as a model system to explore the underlying in vivo mechanism of tumor metastasis, we performed a detailed study of the pathology of epithelial tumor dissemination and investigated the spatial and temporal pattern of tumor cell migration and invasion using macroand microscopic methods
We discovered that the appearance of secondary tumors gradually radiates away from the primary tumors in the eye-antennal disc, suggesting a more directed migration rather than the hemolymph being the main route for metastasis
Summary
Targeted cell migration and invasion play important roles in a variety of biological and disease processes. This phenomenon is exemplified by organotropic metastasis in cancer progression. Tumor metastasis is the leading cause of death for cancer patients (Lambert et al, 2017). A fundamental feature of metastasis is the ability of distinctive tumor types to colonize different organ sites, which depends on the inherent properties of the tumor cells and their interaction with the host tissue. The mechanism of organotropic metastasis is not well delineated. Deciphering the underlying molecular mechanism(s) of interactions between tumor cells and secondary host tissue is essential for our understanding of metastasis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
