ArticleOncogene2014
Early epigenetic downregulation of WNK2 kinase during pancreatic ductal adenocarcinoma development.
Article in Oncogene, 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, 38 citations in OpenAlex.
- WNK2 oncogenicity revealed by the discovery and functional characterization of novel gene isoforms in MYD88 mutated Waldenström's Macroglobulinemia.Blood cancer journal · 2026Article
- Cooperation of Transcription Factor PAX6 with Chromatin-Remodeling Complex BAF During Embryonic Development in Mammals.Cellular and molecular neurobiology · 2026Review
- Article
- PAX6-WNK2 Axis Governs Corneal Epithelial Homeostasis.Investigative ophthalmology & visual science · 2024Article
- Germline mutations inJournal of medical genetics · 2023Article
- Pancreatic Cancer: Genetic Conditions and Epigenetic Alterations.Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2023Review
- Scaffolding Protein Connector Enhancer of Kinase Suppressor of Ras 1 (CNKSR1) Regulates MAPK Inhibition Responsiveness in Pancreas Cancer via Crosstalk with AKT Signaling.Molecular cancer research : MCR · 2023Article
- Epigenetic reprogramming in pancreatic premalignancy and clinical implications.Frontiers in oncology · 2023Review
- An update regarding the role of WNK kinases in cancer.Cell death & disease · 2022Review
- CCT and CCT-Like Modular Protein Interaction Domains in WNK Signaling.Molecular pharmacology · 2022Review
- Whole-Genome DNA Methylation Sequencing Reveals Epigenetic Changes in Myelodysplastic Syndromes.Frontiers in oncology · 2022Article
- Adult-type granulosa cell tumor of the ovary: a FOXL2-centric disease.The journal of pathology. Clinical research · 2021Article
- LINC00858 knockdown inhibits gastric cancer cell growth and induces apoptosis through reducing WNK2 promoter methylation.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- Long non-coding RNA LINC00858 exerts a tumor-promoting role in colon cancer via HNF4α and WNK2 regulation.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- Epigenetic Mechanisms of Pancreatobiliary Fibrosis.Current treatment options in gastroenterology · 2019Review
- Article
- WNK4 is an Adipogenic Factor and Its Deletion Reduces Diet-Induced Obesity in Mice.EBioMedicine · 2017Article
- Pancreatic Cancer, A Mis-interpreter of the Epigenetic Language.The Yale journal of biology and medicine · 2016Review
- Molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer.Molecular biology of the cell · 2016Article
- [Pancreatic acinar neoplasms : Comparative molecular characterization].Der Pathologe · 2016Review
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is usually incurable. Contrary to genetic mechanisms involved in PDAC pathogenesis, epigenetic alterations are ill defined. Here, we determine the contribution of epigenetically silenced genes to the development of PDAC. We analyzed enriched, highly methylated DNAs from PDACs, chronic pancreatitis (CP) and normal tissues using CpG island microarrays and identified WNK2 as a prominent candidate tumor suppressor gene being downregulated early in PDAC development. WNK2 was further investigated in tissue microarrays, methylation analysis of early pancreatic intraepithelial neoplasia (PanIN), mouse models for PDAC and pancreatitis, re-expression studies after demethylation, and cell growth assays using WNK2 overexpression. Demethylation assays confirmed the link between methylation and expression. WNK2 hypermethylation was higher in tumor than in surrounding inflamed tissues and was observed in PanIN lesions as well as in a PDAC mouse model. WNK2 mRNA and protein expressions were lower in PDAC and CP compared with normal tissues both in patients and mouse models. Overexpression of WNK2 led to reduced cell growth, and WNK2 expression in tissues correlated negatively with pERK1/2 expression, a downstream target of WNK2 responsible for cell proliferation. Downregulation of WNK2 by promoter hypermethylation occurs early in PDAC pathogenesis and may support tumor cell growth via the ERK-MAPK pathway.
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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.