Cytolethal Distending Toxin Modulates Cell Differentiation and Elicits Epithelial to Mesenchymal Transition.

Autor:	Azzi-Martin L; Bordeaux Institute of Oncology, UMR1312, INSERM, University of Bordeaux, Bordeaux, France.; Unité de Formation et de Recherche des Sciences Médicales, University of Bordeaux, Bordeaux, France., Touffait-Calvez V; Bordeaux Institute of Oncology, UMR1312, INSERM, University of Bordeaux, Bordeaux, France., Everaert M; Bordeaux Institute of Oncology, UMR1312, INSERM, University of Bordeaux, Bordeaux, France., Jia R; Bordeaux Institute of Oncology, UMR1312, INSERM, University of Bordeaux, Bordeaux, France., Sifré E; Bordeaux Institute of Oncology, UMR1312, INSERM, University of Bordeaux, Bordeaux, France., Seeneevassen L; Bordeaux Institute of Oncology, UMR1312, INSERM, University of Bordeaux, Bordeaux, France., Varon C; Bordeaux Institute of Oncology, UMR1312, INSERM, University of Bordeaux, Bordeaux, France.; Unité de Formation et de Recherche des Sciences Médicales, University of Bordeaux, Bordeaux, France., Dubus P; Bordeaux Institute of Oncology, UMR1312, INSERM, University of Bordeaux, Bordeaux, France.; Unité de Formation et de Recherche des Sciences Médicales, University of Bordeaux, Bordeaux, France.; Institut de Pathologie et de Biologie du Cancer, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France., Ménard A; Bordeaux Institute of Oncology, UMR1312, INSERM, University of Bordeaux, Bordeaux, France.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2024 Jun 14; Vol. 229 (6), pp. 1688-1701.
DOI:	10.1093/infdis/jiae105
Abstrakt:	Background: The bacterial genotoxin, cytolethal distending toxin (CDT), causes DNA damage in host cells, a risk factor for carcinogenesis. Previous studies have shown that CDT induces phenotypes reminiscent of epithelial to mesenchymal transition (EMT), a process involved in cancer initiation and progression. Methods: We investigated different steps of EMT in response to Helicobacter hepaticus CDT and its active CdtB subunit using in vivo and in vitro models. Results: Most of the steps of the EMT process were induced by CDT/CdtB and observed throughout the study in murine and epithelial cell culture models. CdtB induced cell-cell junction disassembly, causing individualization of cells and acquisition of a spindle-like morphology. The key transcriptional regulators of EMT (SNAIL and ZEB1) and some EMT markers were upregulated at both RNA and protein levels in response to CDT/CdtB. CdtB increased the expression and proteolytic activity of matrix metalloproteinases, as well as cell migration. A range of these results were confirmed in Helicobacter hepaticus-infected and xenograft murine models. In addition, colibactin, a genotoxic metabolite produced by Escherichia coli, induced EMT-like effects in cell culture. Conclusions: Overall, these data show that infection with genotoxin-producing bacteria elicits EMT process activation, supporting their role in tumorigenesis. Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu