Concomitant Notch activation and p53 deletion trigger epithelial-to-mesenchymal transition and metastasis in mouse gut - Centre René Huguenin
Article Dans Une Revue Nature Communications Année : 2014

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

Cédric Barrière
  • Fonction : Auteur
Fatima El Marjou
  • Fonction : Auteur
Lev Stimmer
  • Fonction : Auteur
Silvina dos Reis Tavares
  • Fonction : Auteur
Giuseppe-Fulvio Boccia
  • Fonction : Auteur
Didier Meseure
  • Fonction : Auteur
  • PersonId : 974895
Silvia Fre
  • Fonction : Auteur
Loredana Martignetti
  • Fonction : Auteur
Patricia Legoix-Né
  • Fonction : Auteur
  • PersonId : 874626
Elodie Girard
Luc Fetler
  • Fonction : Auteur
Andrei Zinovyev

Résumé

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.
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hal-01712223 , version 1 (08-06-2021)

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Maia Chanrion, Inna Kuperstein, Cédric Barrière, Fatima El Marjou, David Cohen, et al.. Concomitant Notch activation and p53 deletion trigger epithelial-to-mesenchymal transition and metastasis in mouse gut. Nature Communications, 2014, 5, pp.5005. ⟨10.1038/ncomms6005⟩. ⟨hal-01712223⟩
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