Observational studyCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2014
The paracrine hormone for the GUCY2C tumor suppressor, guanylin, is universally lost in colorectal cancer.
Observational study in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Guanylate cyclase-C Signaling Axis as a theragnostic target in colorectal cancer: a systematic review of literature.Frontiers in oncology · 2023Pooled it
- Barriers and Blueprints: Next-Generation Engineering Strategies for CAR-T Cell Therapy in Gastrointestinal Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Construction and Evaluation of Guanylyl Cyclase C-Specific Antibody for Noninvasive Diagnosis and Targeted Therapy of Colorectal Cancer.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Article
- Image-guided therapy of colorectal cancer using a zirconium coordinated nanosensitizer.Journal of nanobiotechnology · 2025Article
- MUC1-Driven Guanylin Gene Delivery via Succinylated PEI-9 Nanocarrier for Colorectal Cancer Treatment: An in Silico and In vitro Study.Advanced pharmaceutical bulletin · 2025Article
- Proteogenomic characterization of primary colorectal cancer and metastatic progression identifies proteome-based subtypes and signatures.Cell reports · 2024Article
- Identification of GUCA2A and COL3A1 as prognostic biomarkers in colorectal cancer by integrating analysis of RNA-Seq data and qRT-PCR validation.Scientific reports · 2023Article
- Type-2 cGMP-dependent protein kinase suppresses proliferation and carcinogenesis in the colon epithelium.Carcinogenesis · 2022Article
- Microbiota and Transcriptomic Effects of an Essential Oil Blend and Its Delivery Route Compared to an Antibiotic Growth Promoter in Broiler Chickens.Microorganisms · 2022Article
- Inhibition of Colon Cancer Cell Growth by Phosphodiesterase Inhibitors Is Independent of cGMP Signaling.The Journal of pharmacology and experimental therapeutics · 2022Article
- A β-Catenin-TCF-Sensitive Locus Control Region Mediates GUCY2C Ligand Loss in Colorectal Cancer.Cellular and molecular gastroenterology and hepatology · 2022Article
- Current Trends in IBD-Development of Mucosal-Based Biomarkers and a Novel Minimally Invasive Recoverable Sampling System.Inflammatory bowel diseases · 2021Article
- Sphingomyelin nanosystems loaded with uroguanylin and etoposide for treating metastatic colorectal cancer.Scientific reports · 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
- The Importance of Sex in the Discovery of Colorectal Cancer Prognostic Biomarkers.International journal of molecular sciences · 2021Article
- GUCY2C as a biomarker to target precision therapies for patients with colorectal cancer.Expert review of precision medicine and drug development · 2021Article
- An update on guanylyl cyclase C in the diagnosis, chemoprevention, and treatment of colorectal cancer.Expert review of clinical pharmacology · 2020Review
- Silencing the intestinal GUCY2C tumor suppressor axis requiresCancer biology & therapy · 2020Article
- APC-β-catenin-TCF signaling silences the intestinal guanylin-GUCY2C tumor suppressor axis.Cancer biology & therapy · 2020Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAlthough colorectal cancer is a disease characterized by sequential accumulation of mutations in epithelial cells, mechanisms leading to genomic vulnerability contributing to tumor initiation remain undefined. GUCY2C has emerged as an intestine-specific tumor suppressor controlling epithelial homeostasis through circuits canonically disrupted in cancer. Surprisingly, the GUCY2C tumor suppressor is universally overexpressed by human colorectal cancer cells. This apparent paradox likely reflects silencing of GUCY2C through loss of its paracrine hormone guanylin. Here, we quantified expression of guanylin mRNA and protein in tumors and normal epithelia from patients with colorectal cancer.
methodsGuanylin mRNA was quantified in tumors and normal adjacent epithelia from 281 patients by the reverse transcriptase-polymerase chain reaction. Separately, the guanylin protein was quantified by immunohistochemistry in 54 colorectal tumors and 30 specimens of normal intestinal epithelium.
resultsGuanylin mRNA in colorectum varied more than a 100-fold across the population. Guanylin mRNA was reduced 100- to 1,000-fold in >85% of tumors compared with matched normal adjacent mucosa (P < 0.001). Loss of guanylin mRNA was greatest in tumors from patients <50 years old (P < 0.005) and with the highest expression in normal adjacent mucosa (Spearman correlation coefficient = 0.61; P < 0.001). In a separate validation cohort, guanylin protein was detected in all 30 normal colorectal mucosa specimens, but in none of 54 colorectal tumors.
conclusionsColorectal cancer may initiate as a disease of paracrine hormone insufficiency through loss of guanylin expression, silencing the GUCY2C tumor suppressor and disrupting homeostatic mechanisms regulating colorectal epithelia cells. IMPACT: Intestinal tumorigenesis may be prevented by oral GUCY2C hormone replacement therapy.
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