Spz/Toll-6 signal guides organotropic metastasis in Drosophila
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 Drosophil...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Book |
| Published: |
The Company of Biologists,
2019-10-01T00:00:00Z.
|
| Subjects: | |
| Online Access: | Connect to this object online. |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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-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. |
|---|---|
| Item Description: | 1754-8403 1754-8411 10.1242/dmm.039727 |