ArticleCancer prevention research (Philadelphia, Pa.)2011
CYLD inhibits tumorigenesis and metastasis by blocking JNK/AP1 signaling at multiple levels.
Article in Cancer prevention research (Philadelphia, Pa.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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
26 citing papers in PubMed, 48 citations in OpenAlex.
- CYLD Alterations Are Associated With Metastasis and Poor Prognosis in Human Papilloma Virus-Positive Head and Neck Cancer.Head & neck · 2025Article
- UBE2N Is Essential for Maintenance of Skin Homeostasis and Suppression of Inflammation.The Journal of investigative dermatology · 2024Article
- Review
- The role of ubiquitination in health and disease.MedComm · 2024Review
- UBE2N is essential for maintenance of skin homeostasis and suppression of inflammation.bioRxiv : the preprint server for biology · 2023Article
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Repressive Control of Keratinocyte Cytoplasmic Inflammatory Signaling.International journal of molecular sciences · 2023Review
- CYLD in health and disease.Disease models & mechanisms · 2023Review
- MALT1-dependent cleavage of CYLD promotes NF-κB signaling and growth of aggressive B-cell receptor-dependent lymphomas.Blood cancer journal · 2023Article
- A map of cis-regulatory modules and constituent transcription factor binding sites in 80% of the mouse genome.BMC genomics · 2022Article
- Role of K63-linked ubiquitination in cancer.Cell death discovery · 2022Review
- The role of ubiquitination and deubiquitination in tumor invasion and metastasis.International journal of biological sciences · 2022Review
- CYLD Inhibits the Development of Skin Squamous Cell Tumors in Immunocompetent Mice.International journal of molecular sciences · 2021Article
- Down-regulation of cylindromatosis protein phosphorylation by BTK inhibitor promotes apoptosis of non-GCB-diffuse large B-cell lymphoma.Cancer cell international · 2021Article
- CYLD Alterations in the Tumorigenesis and Progression of Human Papillomavirus-Associated Head and Neck Cancers.Molecular cancer research : MCR · 2021Review
- NF-κB: At the Borders of Autoimmunity and Inflammation.Frontiers in immunology · 2021Review
- Review
- Article
- Proteomics characterisation of central nervous system metastasis biomarkers in triple negative breast cancer.Ecancermedicalscience · 2019Article
- The tumour suppressor CYLD regulates the p53 DNA damage response.Nature communications · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
CYLD has been recognized as a tumor suppressor due to its dominant genetic linkage to multiple types of epidermal tumors and a range of other cancers. The molecular mechanisms governing CYLD control of skin cancer are still unclear. Here, we showed that K14-driven epidermal expression of a patient-relevant and catalytically deficient CYLD truncated mutant (CYLD(m)) sensitized mice to skin tumor development in response to 7,12-dimethylbenz[α]anthracene (DMBA)/(12-O-tetradecanoylphorbol-13-acetate) TPA challenge. Tumors developed on transgenic mice were prone to malignant progression and lymph node metastasis and displayed increased activation of c-Jun-NH2-kinase (JNK) and the downstream c-Jun and c-Fos proteins. Most importantly, topical application of a pharmacologic JNK inhibitor significantly reduced tumor development and abolished metastasis in the transgenic mice. Further in line with these animal data, exogenous expression of CYLD(m) in A431, a human squamous cell carcinoma (SCC) cell line, markedly enhanced cell growth, migration, and subcutaneous tumor growth in an AP1-depdendent manner. In contrast, expression of the wild-type CYLD inhibited SCC tumorigenesis and AP1 function. Most importantly, CYLD(m) not only increased JNK activation but also induced an upregulation of K63 ubiquitination on both c-Jun and c-Fos, leading to sustained AP1 activation. Our findings uncovered c-Jun and c-Fos as novel CYLD targets and underscore that CYLD controls epidermal tumorigenesis through blocking the JNK/AP1 signaling pathway at multiple levels.
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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.