Next Article in Journal
α-Conotoxin Decontamination Protocol Evaluation: What Works and What Doesn’t
Next Article in Special Issue
The Heat-Stable Enterotoxin Receptor, Guanylyl Cyclase C, as a Pharmacological Target in Colorectal Cancer Immunotherapy: A Bench-to-Bedside Current Report
Previous Article in Journal
Does the Host Contribute to Modulation of Mycotoxin Production by Fruit Pathogens?
Previous Article in Special Issue
Reduced Enterotoxin D Formation on Boiled Ham in Staphylococcus aureus Δagr Mutant
Article Menu
Issue 9 (September) cover image

Export Article

Open AccessFeature PaperArticle
Toxins 2017, 9(9), 279; doi:10.3390/toxins9090279

ST-Producing E. coli Oppose Carcinogen-Induced Colorectal Tumorigenesis in Mice

1
Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USA
2
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32611, USA
3
University of Illinois Chicago School of Medicine, Chicago, IL 60612, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Yukako Fujinaga
Received: 15 August 2017 / Revised: 31 August 2017 / Accepted: 6 September 2017 / Published: 12 September 2017
(This article belongs to the Special Issue Heat-Stable Enterotoxins)
View Full-Text   |   Download PDF [2186 KB, uploaded 12 September 2017]   |  

Abstract

There is a geographic inequality in the incidence of colorectal cancer, lowest in developing countries, and greatest in developed countries. This disparity suggests an environmental contribution to cancer resistance in endemic populations. Enterotoxigenic bacteria associated with diarrheal disease are prevalent in developing countries, including enterotoxigenic E. coli (ETEC) producing heat-stable enterotoxins (STs). STs are peptides that are structurally homologous to paracrine hormones that regulate the intestinal guanylyl cyclase C (GUCY2C) receptor. Beyond secretion, GUCY2C is a tumor suppressor universally silenced by loss of expression of its paracrine hormone during carcinogenesis. Thus, the geographic imbalance in colorectal cancer, in part, may reflect chronic exposure to ST-producing organisms that restore GUCY2C signaling silenced by hormone loss during transformation. Here, mice colonized for 18 weeks with control E. coli or those engineered to secrete ST exhibited normal growth, with comparable weight gain and normal stool water content, without evidence of secretory diarrhea. Enterotoxin-producing, but not control, E. coli, generated ST that activated colonic GUCY2C signaling, cyclic guanosine monophosphate (cGMP) production, and cGMP-dependent protein phosphorylation in colonized mice. Moreover, mice colonized with ST-producing E. coli exhibited a 50% reduction in carcinogen-induced colorectal tumor burden. Thus, chronic colonization with ETEC producing ST could contribute to endemic cancer resistance in developing countries, reinforcing a novel paradigm of colorectal cancer chemoprevention with oral GUCY2C-targeted agents. View Full-Text
Keywords: enterotoxigenic E. coli; heat-stable enterotoxins; azoxymethane; colorectal cancer; GUCY2C-cGMP axis; chemoprevention enterotoxigenic E. coli; heat-stable enterotoxins; azoxymethane; colorectal cancer; GUCY2C-cGMP axis; chemoprevention
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Li, P.; Lin, J.E.; Snook, A.E.; Waldman, S.A. ST-Producing E. coli Oppose Carcinogen-Induced Colorectal Tumorigenesis in Mice. Toxins 2017, 9, 279.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top