Collective cell migration and metastases induced by an epithelial-to-mesenchymal transition in Drosophila intestinal tumors

Kyra Campbell (), Fabrizio Rossi, Jamie Adams, Ioanna Pitsidianaki, Francisco M. Barriga, Laura Garcia-Gerique, Eduard Batlle, Jordi Casanova and Andreu Casali ()
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Kyra Campbell: University of Sheffield
Fabrizio Rossi: The Barcelona Institute of Science and Technology
Jamie Adams: University of Sheffield
Ioanna Pitsidianaki: University of Sheffield
Francisco M. Barriga: Memorial Sloan-Kettering Cancer Center
Laura Garcia-Gerique: Fundació Sant Joan de Déu
Eduard Batlle: The Barcelona Institute of Science and Technology
Jordi Casanova: The Barcelona Institute of Science and Technology
Andreu Casali: Institut de Recerca Biomèdica de Lleida Fundació Dr. Pifarré (IRBLleida)

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract Metastasis underlies the majority of cancer-related deaths yet remains poorly understood due, in part, to the lack of models in vivo. Here we show that expression of the EMT master inducer Snail in primary adult Drosophila intestinal tumors leads to the dissemination of tumor cells and formation of macrometastases. Snail drives an EMT in tumor cells, which, although retaining some epithelial markers, subsequently break through the basal lamina of the midgut, undergo a collective migration and seed polyclonal metastases. While metastases re-epithelialize over time, we found that early metastases are remarkably mesenchymal, discarding the requirement for a mesenchymal-to-epithelial transition for early stages of metastatic growth. Our results demonstrate the formation of metastases in adult flies, and identify a key role for partial-EMTs in driving it. This model opens the door to investigate the basic mechanisms underlying metastasis, in a powerful in vivo system suited for rapid genetic and drug screens.

Date: 2019
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DOI: 10.1038/s41467-019-10269-y

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