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Updated: Jan 10, 2026
Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
Published on: October 6, 2014
Cytotoxic Necrotizing Factor 1-producing E. coli Enhance Colorectal Tumorigenesis in ApcMin/+ Mice With Autophagy
Coline Desseux1, Alison Da Silva1, Anaëlle Tassini1
1M2iSH, UMR 1071 Inserm, Université Clermont Auvergne, INRAE USC 1382, CNRH, Clermont-Ferrand, France.
Background:
In patients with colorectal cancer (CRC), intestinal dysbiosis has been observed, with abnormal colonization of the colonic mucosa by pathogenic Escherichia coli strains producing a cyclomodulin named cytotoxic necrotizing factor (CNF). Cyclomodulins are bacterial toxins capable of altering the cell cycle of the infected cell. One of the mechanisms involved in host defense against pathogens and in carcinogenesis is autophagy. Here, we aimed at investigating the role of autophagy in colorectal carcinogenesis in the context of CNF-producing E. coli, designated as CyPEC (cytotoxic necrotizing factor-producing E. coli), infection.
Methods:
ApcMin/+ mice predisposed to CRC development with autophagy deficiency specifically in intestinal epithelial cells (ApcMin/+/Atg16l1ΔIEC) were infected with the clinical 21F8 strain or the mutant 21F8Δcnf1, which does not produce CNF1.
Results:
In ApcMin/+ mice, infection with 21F8 or 21F8Δcnf1 did not have an impact on the number and the size of colonic tumors. However, in ApcMin/+/Atg16l1ΔIEC mice, infection with 21F8 increased number and size of colonic tumors, compared with uninfected or 21F8Δcnf1-infected condition. This increase was CNF1-dependent as it was not observed upon infection with the 21F8Δcnf1 mutant. Mechanistically, the increase in tumorigenesis in ApcMin/+/Atg16l1ΔIEC mice upon 21F8 infection was associated with enhanced proliferation and decreased apoptosis of colonic epithelial cells.
Conclusions:
Our results show that autophagy deficiency could be a genetic susceptibility for the development of CRC in patients with abnormal colonization by CyPEC strains.
