ArticleCancer research2008
Ectopic expression of P-cadherin correlates with promoter hypomethylation early in colorectal carcinogenesis and enhanced intestinal crypt fission in vivo.
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Bone marrow stromal antigen 2 (BST-2) DNA is demethylated in breast tumors and breast cancer cells.PloS one · 2015Pooled it
- Immune-related gene methylation prognostic instrument for stratification and targeted treatment of ovarian cancer patients toward advanced 3PM approach.The EPMA journal · 2024Article
- Microenvironment-induced restoration of cohesive growth associated with focal activation of P-cadherin expression in lobular breast carcinoma metastatic to the colon.The journal of pathology. Clinical research · 2024Article
- CDH3 Is an Effective Serum Biomarker of Colorectal Cancer Distant Metastasis Patients.Journal of Cancer · 2024Article
- MicroRNA 133A Regulates Cell Proliferation, Cell Migration, and Apoptosis in Colorectal Cancer by Suppressing CDH3 Expression.Journal of Cancer · 2023Article
- Regulatory function of DNA methylation mediated lncRNAs in gastric cancer.Cancer cell international · 2022Review
- Article
- Recent progress in DNA methyltransferase inhibitors as anticancer agents.Frontiers in pharmacology · 2022Review
- Screening for Colorectal Cancer Leading into a New Decade: The "Roaring '20s" for Epigenetic Biomarkers?Current oncology (Toronto, Ont.) · 2021Review
- Cancer-Associated Mutations in Normal Colorectal Mucosa Adjacent to Sporadic Neoplasia.Clinical and translational gastroenterology · 2020Observational
- Epigenetics of colorectal cancer: biomarker and therapeutic potential.Nature reviews. Gastroenterology & hepatology · 2020Review
- E-cadherin Beyond Structure: A Signaling Hub in Colon Homeostasis and Disease.International journal of molecular sciences · 2019Review
- An evolutionary perspective on field cancerization.Nature reviews. Cancer · 2018Review
- P-Cadherin (CDH3) is overexpressed in colorectal tumors and has potential as a serum marker for colorectal cancer monitoring.Oncoscience · 2017Article
- Analysis of different components in the peritumoral tissue microenvironment of colorectal cancer: A potential prospect in tumorigenesis.Molecular medicine reports · 2016Article
- Transcriptomic profiling of urine extracellular vesicles reveals alterations of CDH3 in prostate cancer.Oncotarget · 2016Article
- Significance of P-cadherin overexpression and possible mechanism of its regulation in intrahepatic cholangiocarcinoma and pancreatic cancer.Cancer science · 2015Article
- Expression changes of cell-cell adhesion-related genes in colorectal tumors.Oncology letters · 2015Article
- Field cancerisation in colorectal cancer: a new frontier or pastures past?World journal of gastroenterology · 2015Review
- Cell adhesion and urothelial bladder cancer: the role of cadherin switching and related phenomena.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2015Review
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
Abstract
P-cadherin is normally expressed in the basal layer of squamous epithelia and absent from the healthy intestine and colon. We have previously shown it to be expressed in all inflamed, hyperplastic, and dysplastic intestinal and colonic mucosa. This study aimed to better understand the mechanisms controlling the expression of P-cadherin and the biological effects of its ectopic presence in the intestine and colon. We investigated the CpG methylation status of the P-cadherin (CDH3) promoter and P-cadherin mRNA and protein expression in cases of familial and sporadic colorectal cancer (CRC). The CDH3 promoter was hypomethylated in colonic aberrant crypt foci, in CRC, and, occasionally, in the normal epithelium adjacent to cancer, demonstrating a potential "field effect" of cancerization. The hypomethylation was also associated with induction of P-cadherin expression in the neoplastic colon (P < 0.0001). We then created transgenic mice that overexpressed P-cadherin specifically in the intestinal and colonic epithelium under the liver fatty acid binding protein promoter. Forced ectopic expression of P-cadherin accompanied by indomethacin-induced inflammation resulted in a 3-fold higher crypt fission rate within the small and large intestines in the homozygous mice compared with the wild-type animals (P < 0.02). We conclude that epigenetic demethylation of the P-cadherin promoter in the human intestine permits its ectopic expression very early in the colorectal adenoma-carcinoma sequence and persists during invasive cancer. Induced P-cadherin expression, especially in mucosal damage, leads to an increased rate of crypt fission, a common feature of clonal expansion in gastrointestinal dysplasia.
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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.