Title :

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

Author(s) :

Levy, Jonathan [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Cacheux, Walfran [Auteur]
Institut Curie [Paris]
Institut Cochin [UMR_S567 / UMR 8104]
Bara, Medhi Ait [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
L'Hermitte, Antoine [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Lepage, Patricia [Auteur]
MICrobiologie de l'ALImentation au Service de la Santé [MICALIS]
Fraudeau, Marie [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Trentesaux, Coralie [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Lemarchand, Julie [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Durand, Aurélie [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Crain, Anne-Marie [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Université Paris Diderot - Paris 7 - UFR Sciences du Vivant [UPD7 UFR Sciences du Vivant]
Marchiol, Carmen [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Renault, Gilles [Auteur]
Université Paris Descartes - Paris 5 [UPD5]
Dumont, Florent [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Letourneur, Franck [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Delacres, Myriam [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Schmitt, Alain [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Terris, Benoît [Auteur]
AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris]
Université Paris Descartes - Paris 5 [UPD5]
Perret, Christine [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Chamaillard, Mathias []
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Couty, Jean-Pierre []
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Université Paris Diderot - Paris 7 - UFR Sciences du Vivant [UPD7 UFR Sciences du Vivant]
Romagnolo, Béatrice [Auteur correspondant]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]

Journal title :

Nature Cell Biology

Pages :

1062-1085

Publisher :

Nature Publishing Group

Publication date :

2015

ISSN :

1465-7392

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL