Recent studies suggest that colonization of colonic mucosa by pathogenic Escherichia coli could be involved in the development of colorectal cancer (CRC), especially through the production of genotoxins such as colibactin and/or by interfering with the DNA mismatch repair (MMR) pathway that leads to microsatellite instability (MSI). The present study, performed on 88 CRC patients, revealed a significant increase in E. coli colonization in the MSI CRC phenotype. In the same way, E. coli persistence and internalization were increased in vitro in MMR-deficient cells. Moreover, we demonstrated that colibactin-producing E. coli induce inhibition of the mutL homologue 1 (MLH1) MMR proteins, which could lead to genomic instability. However, colibactin-producing E. coli were more frequently identified in microsatellite stable (MSS) CRC. The present study suggests differences in the involvement of colibactin-producing E. coli in colorectal carcinogenesis according to the CRC phenotype. Further host–pathogen interactions studies should take into account CRC phenotypes.
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Phase contrast microscopy showing primary human mesangial cells in culture. Quantification of cell area showed that exposure of mesangial cells to the pro-fibrotic growth factor (TGF-β1) induced morphological cell expansion and hypertrophy, which was reversed following the overexpression of miR-378. Interestingly, transfection of a miR-378 inhibitor induced the expansion of mesangial cells, highlighting the regulatory role of miR-378 in mesangial hypertrophy. Please see the article by Wang et al. (pages 411-423).
Research Article|
March 06 2017
Interactions between microsatellite instability and human gut colonization by Escherichia coli in colorectal cancer
Johan Gagnière;
Johan Gagnière
1UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France
2INRA USC-2018, 63000 Clermont-Ferrand, France
3Department of Digestive Surgery, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France
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Virginie Bonnin;
Virginie Bonnin
1UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France
2INRA USC-2018, 63000 Clermont-Ferrand, France
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Anne-Sophie Jarrousse;
Anne-Sophie Jarrousse
4Department of Pathology, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France
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Emilie Cardamone;
Emilie Cardamone
1UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France
2INRA USC-2018, 63000 Clermont-Ferrand, France
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Allison Agus;
Allison Agus
1UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France
2INRA USC-2018, 63000 Clermont-Ferrand, France
5Department of Oncogenetic, Centre Jean Perrin, 63000 Clermont-Ferrand, France
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Nancy Uhrhammer;
Nancy Uhrhammer
5Department of Oncogenetic, Centre Jean Perrin, 63000 Clermont-Ferrand, France
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Pierre Sauvanet;
Pierre Sauvanet
1UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France
2INRA USC-2018, 63000 Clermont-Ferrand, France
3Department of Digestive Surgery, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France
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Pierre Déchelotte;
Pierre Déchelotte
4Department of Pathology, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France
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Nicolas Barnich;
Nicolas Barnich
1UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France
2INRA USC-2018, 63000 Clermont-Ferrand, France
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Richard Bonnet;
Richard Bonnet
1UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France
2INRA USC-2018, 63000 Clermont-Ferrand, France
6Department of Bacteriology, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France
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Denis Pezet;
Denis Pezet
1UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France
2INRA USC-2018, 63000 Clermont-Ferrand, France
3Department of Digestive Surgery, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France
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Mathilde Bonnet
1UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France
2INRA USC-2018, 63000 Clermont-Ferrand, France
Correspondence: Mathilde Bonnet ([email protected])
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Publisher: Portland Press Ltd
Received:
November 17 2016
Revision Received:
January 11 2017
Accepted:
January 16 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (6): 471–485.
Article history
Received:
November 17 2016
Revision Received:
January 11 2017
Accepted:
January 16 2017
Citation
Johan Gagnière, Virginie Bonnin, Anne-Sophie Jarrousse, Emilie Cardamone, Allison Agus, Nancy Uhrhammer, Pierre Sauvanet, Pierre Déchelotte, Nicolas Barnich, Richard Bonnet, Denis Pezet, Mathilde Bonnet; Interactions between microsatellite instability and human gut colonization by Escherichia coli in colorectal cancer. Clin Sci (Lond) 1 March 2017; 131 (6): 471–485. doi: https://doi.org/10.1042/CS20160876
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