Spz/Toll-6 signal guides organotropic metastasis in Drosophila

• Main Authors: Ketu Mishra-Gorur (Author), Daming Li (Author), Xianjue Ma (Author), Yanki Yarman (Author), Lei Xue (Author), Tian Xu (Author)
• Format: Book
• Published: The Company of Biologists, 2019-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1754-8403; 1754-8411; 10.1242/dmm.039727
• Keywords: jnk; tumor; cancer; toll-like receptors; spätzle; cell migration; Medicine; R; Pathology; RB1-214
• Source: Disease Models & Mechanisms, Vol 12, Iss 10 (2019)

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.