ArticleCancer biology & therapy2020
APC-β-catenin-TCF signaling silences the intestinal guanylin-GUCY2C tumor suppressor axis.
Article in Cancer biology & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 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
- Targeting molecular and genetic pathways driving tumorigenesis for precision therapy in colorectal cancer.Cancer biology & therapy · 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
- 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
- Guanylyl cyclase C as a diagnostic and therapeutic target in colorectal cancer.Personalized medicine · 2022Review
- A β-Catenin-TCF-Sensitive Locus Control Region Mediates GUCY2C Ligand Loss in Colorectal Cancer.Cellular and molecular gastroenterology and hepatology · 2022Article
- 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
- 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
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Sporadic colorectal cancer initiates with mutations in APC or its degradation target β-catenin, producing TCF-dependent nuclear transcription driving tumorigenesis. The intestinal epithelial receptor, GUCY2C, with its canonical paracrine hormone guanylin, regulates homeostatic signaling along the crypt-surface axis opposing tumorigenesis. Here, we reveal that expression of the guanylin hormone, but not the GUCY2C receptor, is lost at the earliest stages of transformation in APC-dependent tumors in humans and mice. Hormone loss, which silences GUCY2C signaling, reflects transcriptional repression mediated by mutant APC-β-catenin-TCF programs in the nucleus. These studies support a pathophysiological model of intestinal tumorigenesis in which mutant APC-β-catenin-TCF transcriptional regulation eliminates guanylin expression at tumor initiation, silencing GUCY2C signaling which, in turn, dysregulates intestinal homeostatic mechanisms contributing to tumor progression. They expand the mechanistic paradigm for colorectal cancer from a disease of irreversible mutations in APC and β-catenin to one of guanylin hormone loss whose replacement, and reconstitution of GUCY2C signaling, could prevent tumorigenesis.
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