ArticleCarcinogenesis2013
Deregulation of Wnt/β-catenin signaling through genetic or epigenetic alterations in human neuroendocrine tumors.
Article in Carcinogenesis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 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
53 citing papers in PubMed, 81 citations in OpenAlex.
- Multi-omic profiles of neuroendocrine neoplasms of the pancreas: an integrated landscape.Molecular cancer · 2026Review
- Telotristat ethyl affects tumour-fibroblast crosstalk in small intestinal neuroendocrine tumours.Journal of neuroendocrinology · 2025Article
- Potential of C-X-C-Chemokine-Receptor-Type-4-Directed PET/CT Using [¹⁸F]AlF-NOTA-QHY-04 in Identifying Molecular Subtypes of Small Cell Lung Cancer.Korean journal of radiology · 2025Article
- Genetic insight into lung neuroendocrine tumors: Notch and Wnt signaling pathways as potential targets.Journal of translational medicine · 2025Article
- An Overview of Altered Pathways Associated with Sensitivity to Platinum-Based Chemotherapy in Neuroendocrine Tumors: Strengths and Prospects.International journal of molecular sciences · 2024Review
- Review
- Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation.International journal of molecular sciences · 2024Review
- Everything you ever wanted to know about cancer stem cells in neuroendocrine neoplasms but were afraid to ask.Endocrine oncology (Bristol, England) · 2024Review
- Improving susceptibility of neuroendocrine tumors to radionuclide therapies: personalized approaches towards complementary treatments.Theranostics · 2024Review
- Navigating Tumour Microenvironment and Wnt Signalling Crosstalk: Implications for Advanced Cancer Therapeutics.Cancers · 2023Review
- MicroRNAs associated with postoperative outcomes in patients with limited stage neuroendocrine carcinoma of the esophagus.Oncology letters · 2023Article
- Immuno-histochemical correlation of fibrosis-related markers with the desmoplastic reaction of the mesentery in small intestine neuroendocrine neoplasms.Journal of cancer research and clinical oncology · 2023Article
- Novel preclinical gastroenteropancreatic neuroendocrine neoplasia models demonstrate the feasibility of mutation-based targeted therapy.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- hPGCancers · 2022Article
- G9a: An Emerging Epigenetic Target for Melanoma Therapy.Epigenomes · 2021Article
- Review
- From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?Reviews in endocrine & metabolic disorders · 2021Review
- Wnt/β-Catenin Signaling Regulates CXCR4 Expression and [Diagnostics (Basel, Switzerland) · 2021Article
- Immunoprofiling in Neuroendocrine Neoplasms Unveil Immunosuppressive Microenvironment.Cancers · 2020Article
- Molecular insights into therapeutic promise of targeting of Wnt/β-catenin signaling pathway in obesity.Molecular biology reports · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Carcinoid tumors are rare neuroendocrine tumors (NETs) that are increasing in incidence. Mutation and altered expression of Wnt/β-catenin signaling components have been described in many tumors but have not been well-studied in NETs. Here, we observed accumulation of β-catenin in the cytoplasm and/or nucleus in 25% of clinical NET tissues. By mutational analysis, the mutations of β-catenin (I35S) and APC (E1317Q, T1493T) were identified in NET cells and the tissues. Expression of representative Wnt inhibitors was absent or markedly decreased in BON, a human pancreatic carcinoid cell line; treatment with 5-aza-2'-deoxycytidine (5-aza-CdR) increased expression levels of the Wnt inhibitors. Methylation analyses demonstrated that CpG islands of SFRP-1 and Axin-2 were methylated, whereas the promoters of DKK-1, DKK-3 and WIF-1 were unmethylated in four NET cells. Aberrant methylation of SFRP-1 was particularly observed in most of clinical NET tissues. In addition, the repression of these unmethylated genes was associated with histone H3 lysine 9 dimethylation (H3K9me2) in BON cells. Together, 5-aza-CdR treatment inhibited cell proliferation and decreased the protein levels of H3K9me2 and G9a. Moreover, a novel G9a inhibitor, UNC0638, suppressed BON cell proliferation through inhibition of Wnt/β-catenin pathway. Overexpression of the inhibitory genes, particularly SFRP-1 and WIF-1 in BON cells, resulted in suppression of anchorage-independent growth and inhibition of tumor growth in mice. Our findings suggest that aberrant Wnt/β-catenin signaling, through either mutations or epigenetic silencing of Wnt antagonists, contributes to the pathogenesis and growth of NETs and have important clinical implications for the prognosis and treatment of NETs.
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.