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

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.

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Item Type:	Article
Authors/Creators:	Campbell, K. Rossi, F. Adams, J. Pitsidianaki, I. Barriga, F.M. https://orcid.org/0000-0002-0996-7707 Garcia-Gerique, L. Batlle, E. Casanova, J. https://orcid.org/0000-0001-6121-8589 Casali, A.
Copyright, Publisher and Additional Information:	© 2019 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Dates:	Accepted: 1 May 2019 Published (online): 24 May 2019 Published: 24 May 2019
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield)
Depositing User:	Symplectic Sheffield
Date Deposited:	31 May 2019 13:56
Last Modified:	01 Jun 2019 03:15
Status:	Published
Publisher:	Nature Research (part of Springer Nature)
Refereed:	Yes
Identification Number:	10.1038/s41467-019-10269-y
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:146642

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

Abstract

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