ArticleProceedings of the National Academy of Sciences of the United States of America2003
Bacterial enterotoxins are associated with resistance to colon cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed, 143 citations in OpenAlex.
- GUCY2C reverse transcriptase PCR to stage pN0 colorectal cancer patients.Expert review of molecular diagnostics · 2009Trial
- Gut reactions and gut instincts: regulation of intestinal homeostasis by receptor guanylyl cyclase C (GC-C).The Biochemical journal · 2025Review
- Dandelion root extracts and taraxasterol inhibit LPS‑induced colorectal cancer cell viability by blocking TLR4‑NFκB‑driven ACE2 and TMPRSS2 pathways.Experimental and therapeutic medicine · 2024Article
- A β-Catenin-TCF-Sensitive Locus Control Region Mediates GUCY2C Ligand Loss in Colorectal Cancer.Cellular and molecular gastroenterology and hepatology · 2022Article
- Receptor Guanylyl Cyclase C and Cyclic GMP in Health and Disease: Perspectives and Therapeutic Opportunities.Frontiers in endocrinology · 2022Review
- Changing the locks on intestinal signaling.Cell host & microbe · 2021Article
- Guanylyl cyclase 2C (GUCY2C) in gastrointestinal cancers: recent innovations and therapeutic potential.Expert opinion on therapeutic targets · 2021Review
- Guanylyl cyclase C as a biomarker for immunotherapies for the treatment of gastrointestinal malignancies.Biomarkers in medicine · 2021Review
- Dynamics of picosecond laser ablation for surgical treatment of colorectal cancer.Scientific reports · 2020Article
- APC-β-catenin-TCF signaling silences the intestinal guanylin-GUCY2C tumor suppressor axis.Cancer biology & therapy · 2020Article
- NHERF3 is necessary forAmerican journal of physiology. Cell physiology · 2019Article
- MTissue engineering. Part A · 2019Article
- Review
- The Guanylate Cyclase C-cGMP Signaling Axis Opposes Intestinal Epithelial Injury and Neoplasia.Frontiers in oncology · 2018Review
- GUCY2C maintains intestinal LGR5Oncotarget · 2017Article
- Article
- Guanylate cyclase C as a target for prevention, detection, and therapy in colorectal cancer.Expert review of clinical pharmacology · 2017Review
- GUCY2C ligand replacement to prevent colorectal cancer.Cancer biology & therapy · 2016Review
- Obesity-Induced Colorectal Cancer Is Driven by Caloric Silencing of the Guanylin-GUCY2C Paracrine Signaling Axis.Cancer research · 2016Article
- The paracrine hormone for the GUCY2C tumor suppressor, guanylin, is universally lost in colorectal cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2014Observational
5 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
One half million patients suffer from colorectal cancer in industrialized nations, yet this disease exhibits a low incidence in under-developed countries. This geographic imbalance suggests an environmental contribution to the resistance of endemic populations to intestinal neoplasia. A common epidemiological characteristic of these colon cancer-spared regions is the prevalence of enterotoxigenic bacteria associated with diarrheal disease. Here, a bacterial heat-stable enterotoxin was demonstrated to suppress colon cancer cell proliferation by a guanylyl cyclase C-mediated signaling cascade. The heat-stable enterotoxin suppressed proliferation by increasing intracellular cGMP, an effect mimicked by the cell-permeant analog 8-br-cGMP. The antiproliferative effects of the enterotoxin and 8-br-cGMP were reversed by L-cis-diltiazem, a cyclic nucleotide-gated channel inhibitor, as well as by removal of extracellular Ca(2+), or chelation of intracellular Ca(2+). In fact, both the enterotoxin and 8-br-cGMP induced an L-cis-diltiazem-sensitive conductance, promoting Ca(2+) influx and inhibition of DNA synthesis in colon cancer cells. Induction of this previously unrecognized antiproliferative signaling pathway by bacterial enterotoxin could contribute to the resistance of endemic populations to intestinal neoplasia, and offers a paradigm for targeted prevention and therapy of primary and metastatic colorectal cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.