ArticleCarcinogenesis2014
Occult progression by Apc-deficient intestinal crypts as a target for chemoprevention.
Article in Carcinogenesis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Defining the mucosal ecosystem: epithelial-mesenchymal interdependence in gastrointestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Redefining familial adenomatous polyposis: competition, cooperation, and the path to monoclonality.Familial cancer · 2025Review
- Article
- Long-range organization of intestinal 2D-crypts using exogenous Wnt3a micropatterning.Nature communications · 2025Article
- Combination Chemotherapy of Multidrug-resistant Early-stage Colon Cancer: Determining Optimal Dose Schedules by High-performance Computer Simulation.Cancer research communications · 2023Article
- Article
- Multi-ancestral origin of intestinal tumors: Impact on growth, progression, and drug efficacy.Cancer reports (Hoboken, N.J.) · 2022Article
- Subversion of Niche-Signalling Pathways in Colorectal Cancer: What Makes and Breaks the Intestinal Stem Cell.Cancers · 2021Review
- Analysis of mutations in tumor and normal adjacent tissue via fluorescence detection.Environmental and molecular mutagenesis · 2021Article
- Prevention of Colon Cancer Recurrence From Minimal Residual Disease: Computer Optimized Dose Schedules of Intermittent Apoptotic Adjuvant Therapy.JCO clinical cancer informatics · 2020Article
- Study of Caspase 8 mutation in oral cancer and adjacent precancer tissues and implication in progression.PloS one · 2020Article
- A cancer rainbow mouse for visualizing the functional genomics of oncogenic clonal expansion.Nature communications · 2019Article
- Fisetin and 5-fluorouracil: Effective combination for PIK3CA-mutant colorectal cancer.International journal of cancer · 2019Article
- Expression of PD-L1 and SOX2 during rectal tumourigenesis: Potential mechanisms for immune escape and tumour cell invasion.Oncology letters · 2018Article
- New insights into the earliest stages of colorectal tumorigenesis.Expert review of gastroenterology & hepatology · 2017Review
- Insights on glicentin, a promising peptide of the proglucagon family.Biochemia medica · 2017Review
- Single cell lineage tracing reveals a role for TgfβR2 in intestinal stem cell dynamics and differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Dietary Methyl Donor Depletion Suppresses Intestinal Adenoma Development.Cancer prevention research (Philadelphia, Pa.) · 2016Article
- Understanding Intratumoral Heterogeneity: Lessons from the Analysis of At-Risk Tissue and Premalignant Lesions in the Colon.Cancer prevention research (Philadelphia, Pa.) · 2016Article
- An intact Pms2 ATPase domain is not essential for male fertility.DNA repair · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Although Apc mutation is widely considered an initiating event in colorectal cancer, little is known about the earliest stages of tumorigenesis following sporadic Apc loss. Therefore, we have utilized a novel mouse model that facilitates the sporadic inactivation of Apc via frameshift reversion of Cre in single, isolated cells and subsequently tracks the fates of Apc-deficient intestinal cells. Our results suggest that consistent with Apc being a 'gatekeeper', loss of Apc early in life during intestinal growth leads to adenomas or increased crypt fission, manifested by fields of mutant but otherwise normal-appearing crypts. In contrast, Apc loss occurring later in life has minimal consequences, with mutant crypts being less prone to either increased crypt fission or adenoma formation. Using the stem cell-specific Lgr5-CreER mouse, we generated different sized fields of Apc-deficient crypts via independent recombination events and found that field size correlates with progression to adenoma. To evaluate this early stage prior to adenoma formation as a therapeutic target, we examined the chemopreventive effects of sulindac on Apc-deficient occult crypt fission. We found that sulindac treatment started early in life inhibits the morphologically occult spread of Apc-deficient crypts and thus reduces adenoma numbers. Taken together these results suggest that: (i) earlier Apc loss promotes increased crypt fission, (ii) a field of Apc-deficient crypts, which can form via occult crypt fission or independent neighboring events, is an important intermediate between loss of Apc and adenoma formation and (iii) normal-appearing Apc-deficient crypts are potential unappreciated targets for cancer screening and chemoprevention.
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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.