Intestinal inhibition of <em>Atg7</em> prevents tumour initiation through a microbiome-influenced immune response and suppresses tumour growth - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Nature Cell Biology Année : 2015

Intestinal inhibition of Atg7 prevents tumour initiation through a microbiome-influenced immune response and suppresses tumour growth

Jonathan Levy
  • Fonction : Auteur
Medhi Ait Bara
  • Fonction : Auteur
Antoine L'Hermitte
  • Fonction : Auteur
  • PersonId : 784616
  • IdRef : 196475066
Marie Fraudeau
  • Fonction : Auteur
Julie Lemarchand
  • Fonction : Auteur
Aurélie Durand
  • Fonction : Auteur
Carmen Marchiol
  • Fonction : Auteur
Florent Dumont
Alain Schmitt
  • Fonction : Auteur
Christine Perret
Béatrice Romagnolo
  • Fonction : Auteur correspondant

Résumé

Here, we show that autophagy is activated in the intestinal epithelium in murine and human colorectal cancer and that the conditional inactivation of Atg7 in intestinal epithelial cells inhibits the formation of pre-cancerous lesions in Apc(+/-) mice by enhancing anti-tumour responses. The antibody-mediated depletion of CD8(+) T cells showed that these cells are essential for the anti-tumoral responses mediated by the inhibition of autophagy. We show that Atg7 deficiency leads to intestinal dysbiosis and that the microbiota is required for anticancer responses. In addition, Atg7 deficiency resulted in a stress response accompanied by metabolic defects, AMPK activation and p53-mediated cell-cycle arrest in tumour cells but not in normal tissue. This study reveals that the inhibition of autophagy within the epithelium may prevent the development and progression of colorectal cancer in genetically predisposed patients.
Fichier non déposé

Dates et versions

hal-02637789 , version 1 (28-05-2020)

Identifiants

Citer

Jonathan Levy, Walfran Cacheux, Medhi Ait Bara, Antoine L'Hermitte, Patricia Lepage, et al.. Intestinal inhibition of Atg7 prevents tumour initiation through a microbiome-influenced immune response and suppresses tumour growth. Nature Cell Biology, 2015, 17 (8), pp.1062-1085. ⟨10.1038/ncb3206⟩. ⟨hal-02637789⟩
109 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More