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

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dc.contributor.authorCampbell,Kyra
dc.contributor.authorRossi,Fabrizio
dc.contributor.authorAdams, Jamie
dc.contributor.authorPitsidianaki, Ioanna
dc.contributor.authorBarriga, Francisco M.
dc.contributor.authorGarcia-Gerique, Laura
dc.contributor.authorBatlle, Eduard
dc.contributor.authorCasanova, Jordi
dc.contributor.authorCasali, Andreu
dc.date.accessioned2020-09-02T12:16:17Z
dc.date.available2020-09-02T12:16:17Z
dc.date.issued2019-05-24
dc.date.updated2020-09-02T12:16:17Z
dc.description.abstractMetastasis 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.
dc.description.sponsorshipThis 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).
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1038/s41467-019-10269-y
dc.identifier.idgrec030002
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/10459.1/69454
dc.language.isoeng
dc.publisherNature Research
dc.relationinfo:eu-repo/grantAgreement/MINECO//BFU2014-59781-P/ES/CONTROL HORMONAL DE LA HOMEOSTASIS DE LAS CELULAS MADRE INTESTINALES/
dc.relationinfo:eu-repo/grantAgreement/MINECO//BFU2015-73494-JIN/ES/ANALISIS COMPARATIVO DE LOS ROLES DE SNAIL Y GATA FACTORES EN LA PROGRESION TUMORAL Y METASTASIS/
dc.relationinfo:eu-repo/grantAgreement/MINECO//BFU2015-66488-P/ES/DE LOS GENES A LAS CELULAS Y DE LAS CELULAS A LOS ORGANOS EN MODELOS DE MORFOGENESIS DE DROSOPHILA/
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1038/s41467-019-10269-y
dc.relation.ispartofNature Communications, 2019, vol. 10, núm. 1, p. 2311
dc.rightscc-by (c) Campbell,Kyra et al., 2019
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es
dc.subjectCáncer de colon
dc.subjectDrosophila
dc.subjectEMT
dc.titleCollective cell migration and metastases induced by an epithelial-to-mesenchymal transition in Drosophila intestinal tumors
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
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