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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...

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Autores principales: Mishra-Gorur, Ketu, Li, Daming, Ma, Xianjue, Yarman, Yanki, Xue, Lei, Xu, Tian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826028/
https://www.ncbi.nlm.nih.gov/pubmed/31477571
http://dx.doi.org/10.1242/dmm.039727
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author Mishra-Gorur, Ketu
Li, Daming
Ma, Xianjue
Yarman, Yanki
Xue, Lei
Xu, Tian
author_facet Mishra-Gorur, Ketu
Li, Daming
Ma, Xianjue
Yarman, Yanki
Xue, Lei
Xu, Tian
author_sort Mishra-Gorur, Ketu
collection PubMed
description 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.
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spelling pubmed-68260282019-11-04 Spz/Toll-6 signal guides organotropic metastasis in Drosophila Mishra-Gorur, Ketu Li, Daming Ma, Xianjue Yarman, Yanki Xue, Lei Xu, Tian Dis Model Mech Research Article 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. The Company of Biologists Ltd 2019-10-01 2019-10-07 /pmc/articles/PMC6826028/ /pubmed/31477571 http://dx.doi.org/10.1242/dmm.039727 Text en © 2019. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Mishra-Gorur, Ketu
Li, Daming
Ma, Xianjue
Yarman, Yanki
Xue, Lei
Xu, Tian
Spz/Toll-6 signal guides organotropic metastasis in Drosophila
title Spz/Toll-6 signal guides organotropic metastasis in Drosophila
title_full Spz/Toll-6 signal guides organotropic metastasis in Drosophila
title_fullStr Spz/Toll-6 signal guides organotropic metastasis in Drosophila
title_full_unstemmed Spz/Toll-6 signal guides organotropic metastasis in Drosophila
title_short Spz/Toll-6 signal guides organotropic metastasis in Drosophila
title_sort spz/toll-6 signal guides organotropic metastasis in drosophila
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826028/
https://www.ncbi.nlm.nih.gov/pubmed/31477571
http://dx.doi.org/10.1242/dmm.039727
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