Concomitant Notch activation and p53 deletion trigger epithelial-to-mesenchymal transition and metastasis in mouse gut

Maia Chanrion, Inna Kuperstein, Cédric Barrière, Fatima El Marjou, David Cohen, Danijela Vignjevic, Lev Stimmer, Perrine Paul-Gilloteaux, Ivan Bièche, Silvina Dos Reis Tavares, Giuseppe-Fulvio Boccia, Wulfran Cacheux, Didier Meseure, Silvia Fre, Loredana Martignetti, Patricia Legoix-Né, Elodie Girard, Luc Fetler, Emmanuel Barillot, Daniel Louvard (), Andreï Zinovyev and Sylvie Robine
Additional contact information
Maia Chanrion: Institut Curie, Centre de Recherche
Inna Kuperstein: Institut Curie, Centre de Recherche
Cédric Barrière: Institut Curie, Centre de Recherche
Fatima El Marjou: Institut Curie, Centre de Recherche
David Cohen: Institut Curie, Centre de Recherche
Danijela Vignjevic: Institut Curie, Centre de Recherche
Lev Stimmer: Institut Curie, Centre de Recherche
Perrine Paul-Gilloteaux: Institut Curie, Centre de Recherche
Ivan Bièche: Inserm U735, Hôpital René Huguenin
Silvina Dos Reis Tavares: Institut Curie, Centre de Recherche
Giuseppe-Fulvio Boccia: Institut Curie, Centre de Recherche
Wulfran Cacheux: Institut Curie, Centre Hospitalier
Didier Meseure: Institut Curie, Centre Hospitalier
Silvia Fre: Institut Curie, Centre de Recherche
Loredana Martignetti: Institut Curie, Centre de Recherche
Patricia Legoix-Né: Next-Generation Sequencing Platform, Institut Curie
Elodie Girard: Institut Curie, Centre de Recherche
Luc Fetler: Institut Curie, Centre de Recherche
Emmanuel Barillot: Institut Curie, Centre de Recherche
Daniel Louvard: Institut Curie, Centre de Recherche
Andreï Zinovyev: Institut Curie, Centre de Recherche
Sylvie Robine: Institut Curie, Centre de Recherche

Nature Communications, 2014, vol. 5, issue 1, 1-15

Abstract: Abstract Epithelial-to-mesenchymal transition-like (EMT-like) is a critical process allowing initiation of metastases during tumour progression. Here, to investigate its role in intestinal cancer, we combine computational network-based and experimental approaches to create a mouse model with high metastatic potential. Construction and analysis of this network map depicting molecular mechanisms of EMT regulation based on the literature suggests that Notch activation and p53 deletion have a synergistic effect in activating EMT-like processes. To confirm this prediction, we generate transgenic mice by conditionally activating the Notch1 receptor and deleting p53 in the digestive epithelium (NICD/p53−/−). These mice develop metastatic tumours with high penetrance. Using GFP lineage tracing, we identify single malignant cells with mesenchymal features in primary and metastatic tumours in vivo. The development of such a model that recapitulates the cellular features observed in invasive human colorectal tumours is appealing for innovative drug discovery.

Date: 2014
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms6005 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6005

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms6005

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().