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Nature. 2018 Apr;556(7702):463-468. doi: 10.1038/s41586-018-0040-3. Epub 2018 Apr 18.

Identification of the tumour transition states occurring during EMT.

Author information

1
Laboratory of Stem Cells and Cancer, Université Libre de Buxelles, Brussels, Belgium.
2
Department of Human Genetics, University of Leuven, Leuven, Belgium.
3
Sanger Institute-EBI Single-Cell Genomics Centre, Wellcome Trust Sanger Institute, Hinxton, UK.
4
Laboratory for Molecular Cancer Biology, VIB Center for Cancer Biology, Leuven, Belgium.
5
Pathology Department, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
6
DIAPath, The Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium.
7
Thoracic Surgery, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
8
Gastroenterology Department, Hospital Clínico Universitario "Lozano Blesa", IIS Aragon, Zaragoza, Spain.
9
CIBERehd, IIS Aragón, University of Zaragoza, Zaragoza, Spain.
10
Laboratory for Molecular Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.
11
Laboratory of Stem Cells and Cancer, Université Libre de Buxelles, Brussels, Belgium. cedric.blanpain@ulb.ac.be.
12
WELBIO, Université Libre de Bruxelles, Bruxelles, Belgium. cedric.blanpain@ulb.ac.be.

Abstract

In cancer, the epithelial-to-mesenchymal transition (EMT) is associated with tumour stemness, metastasis and resistance to therapy. It has recently been proposed that, rather than being a binary process, EMT occurs through distinct intermediate states. However, there is no direct in vivo evidence for this idea. Here we screen a large panel of cell surface markers in skin and mammary primary tumours, and identify the existence of multiple tumour subpopulations associated with different EMT stages: from epithelial to completely mesenchymal states, passing through intermediate hybrid states. Although all EMT subpopulations presented similar tumour-propagating cell capacity, they displayed differences in cellular plasticity, invasiveness and metastatic potential. Their transcriptional and epigenetic landscapes identify the underlying gene regulatory networks, transcription factors and signalling pathways that control these different EMT transition states. Finally, these tumour subpopulations are localized in different niches that differentially regulate EMT transition states.

PMID:
29670281
DOI:
10.1038/s41586-018-0040-3
[Indexed for MEDLINE]

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