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Collective cell migration and metastases induced by an epithelial-to-mesenchymal transition in Drosophila intestinal tumors
Campbell,Kyra; Rossi,Fabrizio; Adams, Jamie; Pitsidianaki, Ioanna; Barriga, Francisco M.; Garcia-Gerique, Laura; Batlle, Eduard; Casanova, Jordi; Casali, Andreu
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. This study was supported by grants from the Ministerio de Economía y competitividad (Grant Numbers BFU2014–59781-P (to A.C.), BFU2015–73494-JIN (to K.C.), BFU2015–66488-P (to J.C.)). This work was also supported by the Joseph Steiner Foundation (to E.B.) and a Wellcome Trust/Royal Society Sir Henry Dale Award to K.C. (Grant number R/148777–11–1).
-Cáncer de colon
-Drosophila
-EMT
cc-by (c) Campbell,Kyra et al., 2019
http://creativecommons.org/licenses/by/3.0/es
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Article - Published version
Nature Research
         

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