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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-12

AUTHORS

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, Sylvie Robine

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. More... »

PAGES

5005

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms6005

    DOI

    http://dx.doi.org/10.1038/ncomms6005

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1034291134

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25295490


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    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/ncomms6005'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/ncomms6005'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/ncomms6005'

    RDF/XML is a standard XML format for linked data.

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