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

First Author  Lévy J Year  2015
Journal  Nat Cell Biol Volume  17
Issue  8 Pages  1062-73
PubMed ID  26214133 Mgi Jnum  J:227287
Mgi Id  MGI:5700116 Doi  10.1038/ncb3206
Citation  Levy J, et al. (2015) Intestinal inhibition of Atg7 prevents tumour initiation through a microbiome-influenced immune response and suppresses tumour growth. Nat Cell Biol 17(8):1062-73
abstractText  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.
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