Pro-carcinogenic bacteria have the potential to initiate and/or promote colon cancer, in part via immune mechanisms that are incompletely understood. Using ApcMin mice colonized with the human pathobiont enterotoxigenic Bacteroides fragilis (ETBF) as a model of microbe-induced colon tumorigenesis, we show that the Bacteroides fragilis toxin (BFT) triggers a pro-carcinogenic, multi-step inflammatory cascade requiring IL-17R, NF-κB, and Stat3 signaling in colonic epithelial cells (CECs). Although necessary, Stat3 activation in CECs is not sufficient to trigger ETBF colon tumorigenesis. Notably, IL-17-dependent NF-κB activation in CECs induces a proximal to distal mucosal gradient of C-X-C chemokines, including CXCL1, that mediates the recruitment of CXCR2-expressing polymorphonuclear immature myeloid cells with parallel onset of ETBF-mediated distal colon tumorigenesis. Thus, BFT induces a pro-carcinogenic signaling relay from the CEC to a mucosal Th17 response that results in selective NF-κB activation in distal colon CECs, which collectively triggers myeloid-cell-dependent distal colon tumorigenesis.
Pubmed ID: 29398651 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
A commercial graphing software company that offers scientific software for statistical analyses, curve fitting and data analysis. It offers four programs: Prism, InStat, StatMate and QuickCalcs.
View all literature mentionsThis monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH
View all literature mentionsThis polyclonal targets IL17RA / IL-17RA
View all literature mentionsThis monoclonal targets PARP
View all literature mentionsThis polyclonal targets RELA
View all literature mentionsThis monoclonal targets Actin alpha-Smooth Muscle - Cy3(TM) antibody produced in mouse
View all literature mentionsThis monoclonal targets Human E-Cadherin
View all literature mentionsThis polyclonal targets IL17RA
View all literature mentionsThis monoclonal targets Phospho-Stat3 (Tyr705)
View all literature mentionsThis monoclonal targets IL-17A
View all literature mentionsThis monoclonal targets FOXP3
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD45.2
View all literature mentionsThis monoclonal targets F4/80
View all literature mentionsThis monoclonal targets CD103 (Integrin alpha E)
View all literature mentionsThis monoclonal targets CD86
View all literature mentionsThis monoclonal targets I-A/I-E
View all literature mentionsThis monoclonal targets Ly-6G
View all literature mentionsThis monoclonal targets Ly-6C
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets Rat CD45 V500 Clone 30-F11
View all literature mentionsMicroscope imaging software suite used with Nikon products. NIS-Elements includes software applications for advanced and standard research, documentation, confocal microscopy, and high-content analysis.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsA collection of tools for flow cytometer and application setup, data acquisition, and data analysis that help streamline flow cytometry workflows. It provides features to help users integrate flow systems into new application areas, including index sorting for stem cell and single-cell applications, as well as automation protocols for high-throughput and robotic laboratories.
View all literature mentionsMus musculus with name B6.Cg-Tg(Vil1-cre)997Gum/J from IMSR.
View all literature mentionsMus musculus with name B6.129P2-Lyz2tm1(cre)Ifo/J from IMSR.
View all literature mentionsMus musculus with name B6.129S2-Il6tm1Kopf/J from IMSR.
View all literature mentionsMus musculus with name B6;SJL-Il6ratm1.1Drew/J from IMSR.
View all literature mentionsMus musculus with name B6.129P2(Cg)-Cx3cr1tm1Litt/J from IMSR.
View all literature mentionsMus musculus with name B6.129P2-Cxcr4tm2Yzo/J from IMSR.
View all literature mentionsMus musculus with name B6.129S2(C)-Cxcr2tm1Mwm/J from IMSR.
View all literature mentionsMus musculus with name B6.SJL-Ptprca Pepc/BoyJ from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentions