ArticleMolecular oncology2016
The canonical Wnt pathway regulates the metastasis-promoting mucin MUC4 in pancreatic ductal adenocarcinoma.
Article in Molecular oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Wnt Signalling-Activated EN2 Promotes the Progression of Glioblastoma by Upregulating Fatty Acid Synthesis Metabolism.Journal of cellular and molecular medicine · 2025Article
- MUC4 O-GlcNAcylation Regulates the Epithelial Phenotype in Conjunctival Epithelial Cells.Biochemical genetics · 2025Article
- The multifaceted roles of mucins family in lung cancer: from prognostic biomarkers to promising targets.Frontiers in immunology · 2025Review
- Pyrotinib-based therapeutic approaches for HER2-positive breast cancer: the time is now.Breast cancer research : BCR · 2023Review
- WNT signaling in the tumor microenvironment promotes immunosuppression in murine pancreatic cancer.The Journal of experimental medicine · 2023Article
- Smoking-associated Downregulation of FILIP1L Enhances Lung Adenocarcinoma Progression Through Mucin Production, Inflammation, and Fibrosis.Cancer research communications · 2022Article
- Article
- The role of membrane mucin MUC4 in breast cancer metastasis.Endocrine-related cancer · 2021Review
- WNT as a Driver and Dependency in Cancer.Cancer discovery · 2021Review
- Post-mortem tissue donation programs as platforms to accelerate cancer research.The journal of pathology. Clinical research · 2020Review
- Global analysis of human glycosyltransferases reveals novel targets for pancreatic cancer pathogenesis.British journal of cancer · 2020Article
- MUCIN-4 (MUC4) is a novel tumor antigen in pancreatic cancer immunotherapy.Seminars in immunology · 2020Review
- Article
- Mucins as a New Frontier in Pulmonary Fibrosis.Journal of clinical medicine · 2019Review
- β-Catenin expression is associated with cell invasiveness in pancreatic cancer.The Korean journal of internal medicine · 2019Article
- Possible Molecular Markers for the Diagnosis of Pancreatic Ductal Adenocarcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- MUC4 mucin- a therapeutic target for pancreatic ductal adenocarcinoma.Expert opinion on therapeutic targets · 2017Review
- Bile acids-mediated overexpression of MUC4 via FAK-dependent c-Jun activation in pancreatic cancer.Molecular oncology · 2016Article
- MUC4 is negatively regulated through the Wnt/β-catenin pathway via the Notch effector Hath1 in colorectal cancer.Genes & cancer · 2016Article
- Mucins and Wnt/β-catenin signaling in gastrointestinal cancers: an unholy nexus.Carcinogenesis · 2016Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Aberrant Wnt signaling frequently occurs in pancreatic cancer (PC) and contributes to disease progression/metastases. Likewise, the transmembrane-mucin MUC4 is expressed de novo in early pancreatic intraepithelial neoplasia (PanINs) and incrementally increases with PC progression, contributing to metastasis. To determine the mechanism of MUC4 upregulation in PC, we examined factors deregulated in early PC progression, such as Wnt/β-catenin signaling. MUC4 promoter analysis revealed the presence of three putative TCF/LEF-binding sites, leading us to hypothesize that MUC4 can be regulated by β-catenin. Immunohistochemical (IHC) analysis of rapid autopsy PC tissues showed a correlation between MUC4 and cytosolic/nuclear β-catenin expression. Knock down (KD) of β-catenin in CD18/HPAF and T3M4 cell lines resulted in decreased MUC4 transcript and protein. Three MUC4 promoter luciferase constructs, p3778, p3000, and p2700, were generated. The construct p3778, encompassing the entire MUC4 promoter, elicited increased luciferase activity in the presence of stabilized β-catenin. Mutation of the TCF/LEF site closest to the transcription start site (i.e., -2629/-2612) and furthest from the start site (i.e., -3425/-3408) reduced MUC4 promoter luciferase activity. Transfection with dominant negative TCF4 decreased MUC4 transcript and protein levels. Chromatin immunoprecipitation confirmed enrichment of β-catenin on -2629/-2612 and -3425/-3408 of the MUC4 promoter in CD18/HPAF. Functionally, CD18/HPAF and T3M4 β-catenin KD cells showed decreased migration and decreased Vimentin, N-cadherin, and pERK1/2 expression. Tumorigenicity studies in athymic nude mice showed CD18/HPAF β-catenin KD cells significantly reduced primary tumor sizes and metastases compared to scrambled control cells. We show for the first time that β-catenin directly governs MUC4 in PC.
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