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

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...

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Detalles Bibliográficos
Autores: Campbell,Kyra, Rossi,Fabrizio, Adams, Jamie, Pitsidianaki, Ioanna, Barriga, Francisco M., Garcia-Gerique, Laura, Batlle, Eduard, Casanova, Jordi, Casali, Andreu
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10459.1/69454
Acceso en línea:https://doi.org/10.1038/s41467-019-10269-y
http://hdl.handle.net/10459.1/69454
Access Level:acceso abierto
Palabra clave:Cáncer de colon
Drosophila
EMT
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spelling Collective cell migration and metastases induced by an epithelial-to-mesenchymal transition in Drosophila intestinal tumorsCampbell,KyraRossi,FabrizioAdams, JamiePitsidianaki, IoannaBarriga, Francisco M.Garcia-Gerique, LauraBatlle, EduardCasanova, JordiCasali, AndreuCáncer de colonDrosophilaEMTMetastasis 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).Nature Research2020202020192020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://doi.org/10.1038/s41467-019-10269-yhttp://hdl.handle.net/10459.1/69454http://hdl.handle.net/10459.1/69454reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/grantAgreement/MINECO//BFU2014-59781-Pinfo:eu-repo/grantAgreement/MINECO//BFU2015-73494-JINinfo:eu-repo/grantAgreement/MINECO//BFU2015-66488-PReproducció del document publicat a: https://doi.org/10.1038/s41467-019-10269-yNature Communications, 2019, vol. 10, núm. 1, p. 2311cc-by (c) Campbell,Kyra et al., 2019info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/esoai:recercat.cat:10459.1/694542026-05-29T05:05:01Z
dc.title.none.fl_str_mv Collective cell migration and metastases induced by an epithelial-to-mesenchymal transition in Drosophila intestinal tumors
title Collective cell migration and metastases induced by an epithelial-to-mesenchymal transition in Drosophila intestinal tumors
spellingShingle Collective cell migration and metastases induced by an epithelial-to-mesenchymal transition in Drosophila intestinal tumors
Campbell,Kyra
Cáncer de colon
Drosophila
EMT
title_short Collective cell migration and metastases induced by an epithelial-to-mesenchymal transition in Drosophila intestinal tumors
title_full Collective cell migration and metastases induced by an epithelial-to-mesenchymal transition in Drosophila intestinal tumors
title_fullStr Collective cell migration and metastases induced by an epithelial-to-mesenchymal transition in Drosophila intestinal tumors
title_full_unstemmed Collective cell migration and metastases induced by an epithelial-to-mesenchymal transition in Drosophila intestinal tumors
title_sort Collective cell migration and metastases induced by an epithelial-to-mesenchymal transition in Drosophila intestinal tumors
dc.creator.none.fl_str_mv Campbell,Kyra
Rossi,Fabrizio
Adams, Jamie
Pitsidianaki, Ioanna
Barriga, Francisco M.
Garcia-Gerique, Laura
Batlle, Eduard
Casanova, Jordi
Casali, Andreu
author Campbell,Kyra
author_facet Campbell,Kyra
Rossi,Fabrizio
Adams, Jamie
Pitsidianaki, Ioanna
Barriga, Francisco M.
Garcia-Gerique, Laura
Batlle, Eduard
Casanova, Jordi
Casali, Andreu
author_role author
author2 Rossi,Fabrizio
Adams, Jamie
Pitsidianaki, Ioanna
Barriga, Francisco M.
Garcia-Gerique, Laura
Batlle, Eduard
Casanova, Jordi
Casali, Andreu
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cáncer de colon
Drosophila
EMT
topic Cáncer de colon
Drosophila
EMT
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1038/s41467-019-10269-y
http://hdl.handle.net/10459.1/69454
http://hdl.handle.net/10459.1/69454
url https://doi.org/10.1038/s41467-019-10269-y
http://hdl.handle.net/10459.1/69454
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MINECO//BFU2014-59781-P
info:eu-repo/grantAgreement/MINECO//BFU2015-73494-JIN
info:eu-repo/grantAgreement/MINECO//BFU2015-66488-P
Reproducció del document publicat a: https://doi.org/10.1038/s41467-019-10269-y
Nature Communications, 2019, vol. 10, núm. 1, p. 2311
dc.rights.none.fl_str_mv cc-by (c) Campbell,Kyra et al., 2019
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es
rights_invalid_str_mv cc-by (c) Campbell,Kyra et al., 2019
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812455

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