ArticleInfection and immunity2014
Clostridium difficile toxin A attenuates Wnt/β-catenin signaling in intestinal epithelial cells.
Article in Infection and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Modeling Clostridioides difficile toxin pathogenesis and antiserum protection in an immunocompetent intestine-on-chip platform.Scientific reports · 2026Article
- Mechanisms ofFrontiers in cellular and infection microbiology · 2025Review
- Exploring the Toxin-Mediated Mechanisms inMicroorganisms · 2024Review
- Alterations in the gut microbiota and their metabolites in human intestinal epithelial cells of patients with colorectal cancer.Molecular biology reports · 2024Article
- Crosstalk between PI3K/Akt and Wnt/β-catenin pathways promote colorectal cancer progression regardless of mutational status.Cancer biology & therapy · 2022Article
- Research progress on the relationship between intestinal microecology and intestinal bowel disease.Animal models and experimental medicine · 2022Review
- Human Colon Cancer-Derived Clostridioides difficile Strains Drive Colonic Tumorigenesis in Mice.Cancer discovery · 2022Article
- Review
- Low-density lipoprotein receptor-related protein 1 is a CROPs-associated receptor for Clostridioides infection toxin B.Science China. Life sciences · 2022Article
- The Essential Role of Rac1 Glucosylation inFrontiers in microbiology · 2022Article
- Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection Associates With Functional Alterations in Circulating microRNAs.Gastroenterology · 2021Article
- Article
- Clostridium difficile toxins or infection induce upregulation of adenosine receptors and IL-6 with early pro-inflammatory and late anti-inflammatory pattern.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2020Article
- Article
- Article
- Bacterial Manipulation of Wnt Signaling: A Host-Pathogen Tug-of-Wnt.Frontiers in immunology · 2019Review
- Wnt/β-Catenin Signaling as a Molecular Target by Pathogenic Bacteria.Frontiers in immunology · 2019Review
- Clostridium difficile toxins A and B decrease intestinal SLC26A3 protein expression.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Transforming Growth Factor β1/SMAD Signaling Pathway Activation Protects the Intestinal Epithelium from Clostridium difficile Toxin A-Induced Damage.Infection and immunity · 2017Article
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clostridium difficile toxins A and B (TcdA and TcdB) are homologous glycosyltransferases that inhibit a group of small GTPases within host cells, but several mechanisms underlying their pathogenic activity remain unclear. In this study, we evaluated the effects of TcdA on the Wnt/β-catenin pathway, the major driving force behind the proliferation of epithelial cells in colonic crypts. IEC-6 and RKO cells stimulated with Wnt3a-conditioned medium were incubated with 10, 50, and 100 ng/ml of TcdA for 24 h, resulting in a dose-dependent inhibition of the Wnt signaling, as demonstrated by a T-cell factor (TCF) reporter assay. This was further confirmed by immunofluorescence staining for nuclear localization of β-catenin and Western blotting for β-catenin and c-Myc (encoded by a Wnt target gene). Moreover, our Western blot analysis showed a decrease in the β-catenin protein levels, which was reversed by z-VAD-fmk, a pan-caspase inhibitor. Nonetheless, TcdA was still able to inhibit the Wnt/β-catenin pathway even in the presence of z-VAD-fmk, lithium chloride (a GSK3β inhibitor), or constitutively active β-catenin, as determined by a TCF reporter assay. Furthermore, preincubation of RKO cells with TcdA for 12 h also attenuated Wnt3a-mediated activation of Wnt signaling, suggesting that inactivation of Rho GTPases plays a significant role in that inhibition. Taken together, these findings suggest that attenuation of the Wnt signaling by TcdA is important for TcdA antiproliferative effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.