The cyclin D1 gene is a target of the β-catenin/LEF-1 pathway
Open accessAbstract
β-Catenin plays a dual role in the cell: one in linking the cytoplasmic side of cadherin-mediated cell–cell contacts to the actin cytoskeleton and an additional role in signaling that involves transactivation in complex with transcription factors of the lymphoid enhancing factor (LEF-1) family. Elevated β-catenin levels in colorectal cancer caused by mutations in β-catenin or by the adenomatous polyposis coli molecule, which regulates β-catenin degradation, result in the binding of β-catenin to LEF-1 and increased transcriptional activation of mostly unknown target genes. Here, we show that the cyclin D1 gene is a direct target for transactivation by the β-catenin/LEF-1 pathway through a LEF-1 binding site in the cyclin D1 promoter. Inhibitors of β-catenin activation, wild-type adenomatous polyposis coli, axin, and the cytoplasmic tail of cadherin suppressed cyclin D1 promoter activity in colon cancer cells. Cyclin D1 protein levels were induced by β-catenin overexpression and reduced in cells overexpressing the cadherin cytoplasmic domain. Increased β-catenin levels may thus promote neoplastic conversion by triggering cyclin D1 gene expression and, consequently, uncontrolled progression into the cell cycle.
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Wnt/β-catenin signaling controls the G1/S transition.
“The Wnt/β-catenin signaling pathway is one of the mechanisms known to control G1/S transition (35–38).”
From Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade (2022) · cites this paper as [36]
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Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade
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- Authors
- Shtutman, M., Zhurinsky, J., Simcha, I., Albanese, C., D’Amico, M., Pestell, R., & Ben-Ze’ev, A.
- Affiliations
- Albert Einstein College of Medicine (US)
- Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel; and Department of Medicine and Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1999-05-11
- Volume
- 96
- Issue
- 10
- Pages
- 5522-5527
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC21892
- OpenAlex
- W2109069210
- Cited by
- 2,230
- References
- 2
- Citations by year
- 2026: 21 · 2025: 40 · 2024: 42 · 2023: 49 · 2022: 39 · 2021: 68 · 2020: 69 · 2019: 65 · 2018: 63 · 2017: 93 · 2016: 76 · 2015: 92 · 2014: 104 · 2013: 96 · 2012: 89
- FWCI
- 33.65
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- cyclin D1, β-catenin, LEF1, Wnt signaling, transcriptional activation, cyclin D1 promoter, adenomatous polyposis coli, Axin, colorectal cancer, cell cycle progression
- MeSH terms
- Binding Sites, Colonic Neoplasms, Cytoskeletal Proteins, DNA-Binding Proteins, Humans, Promoter Regions, Genetic, Proteins, Repressor Proteins, Transcription Factors, Transfection, Tumor Cells, Cultured, Signal Transduction, Transcriptional Activation, Trans-Activators, Cadherins, Gene Expression Regulation, Neoplastic, Cyclin D1, Adenomatous Polyposis Coli Protein, beta Catenin, Lymphoid Enhancer-Binding Factor 1, Axin Protein
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