Salmonella protein AvrA activates the STAT3 signaling pathway in colon cancer
Open accessAbstract
Salmonella infection in humans can become chronic, which leads to low-grade persistent inflammation. These chronic infections increase the risk of several gastrointestinal diseases, including cancer. Salmonella AvrA is a multifunctional protein that influences eukaryotic cell pathways by regulating ubiquitination and acetylation. In an animal model, we have demonstrated that infection with AvrA-expressing Salmonella induces beta-catenin signals and enhances colonic tumorigenesis. Beta-catenin signaling is a key player in intestinal proliferation and tumorigenesis. The relative contributions of AvrA-induced proliferation and inflammation on tumorigenesis, however, are unknown. STAT3 is activated in chronically inflamed intestines in human inflammatory bowel diseases and in colitis-associated colon cancer. In the current study, mice were colonized with Salmonella AvrA-sufficient or AvrA-deficient bacterial strains. Then, inflammation-associated colon cancer was induced through the use of azoxymethane/dextran sulfate sodium. We determined that AvrA-expressing bacteria activated the STAT3 pathway, which is predicted to enhance proliferation and promote tumorigenesis. Transcriptional activity of STAT3 and its target genes were upregulated by Salmonella expressing AvrA, thus promoting proliferation and intestinal tumorigenesis. Our findings provide new insights regarding a STAT3-dependent mechanism by which the specific bacterial product AvrA enhances the development of infection-associated colon cancer. These insights might suggest future biomarkers to risk assessment and early detection of infection-related cancer.
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Salmonella's AvrA protein drives inflammation and colon tumor growth through activation of beta-catenin signaling to STAT3.
“The protein AvrA, produced by Salmonella, promotes inflammation and colon tumor development by activating beta-catenin signaling to STAT3.36, 180”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [180]
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Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer
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- Authors
- Lu, R., Wu, S., Zhang, Y.-G., Xia, Y., Zhou, Z., Kato, I., Dong, H., Bissonnette, M., & Sun, J.
- Affiliations
- University of Illinois Chicago (US)
- Rush University (US)
- University of Rochester (US)
- University of Rochester Medicine (US)
- Wayne State University (US)
- Army Medical University (CN)
- University of Chicago (US)
- Corresponding author
- Sun, Jun
- Venue
- Neoplasia
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 18
- Issue
- 5
- Pages
- 307-316
- ISSN
- 1476-5586 (ISSN-L)
- PMC
- PMC4887618
- OpenAlex
- W2403375077
- Cited by
- 99
- References
- 46
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 12 · 2023: 18 · 2022: 6 · 2021: 13 · 2020: 8 · 2019: 9 · 2018: 5 · 2017: 10 · 2016: 1
- FWCI
- 7.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neoplasia (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- American Cancer Society
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
- Keywords
- STAT3 signaling, colon cancer, colitis-associated colorectal cancer, β-catenin signaling, intestinal inflammation, bacterial virulence factors, intestinal proliferation, azoxymethane/dextran sulfate sodium, infection-associated cancer, ubiquitination, acetylation
- MeSH terms
- Animals, Bacterial Proteins, Chronic Disease, Colonic Neoplasms, Disease Models, Animal, Female, Humans, Models, Biological, Salmonella, Salmonella Infections, Signal Transduction, Biomarkers, Cytokines, Cell Line, Tumor, Cell Proliferation, STAT3 Transcription Factor, Mice
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