ArticleScience signaling2013
Epigenetic activation of AP1 promotes squamous cell carcinoma metastasis.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 125 citations in OpenAlex.
- Tissue-specific fibroblast lipid cues impose the rate of epithelial cancer invasion.Nature metabolism · 2026Article
- Impact ofJournal of Cancer · 2026Article
- KDM4A serves as an α-tubulin demethylase regulating microtubule polymerization and cell mitosis.Science advances · 2025Article
- Isoorientin Ameliorates Macrophage Pyroptosis and Atherogenesis by Reducing KDM4A Levels and Promoting SKP1-Cullin1-F-box E3 Ligase-mediated NLRP3 Ubiquitination.Inflammation · 2025Article
- CD44-targeted virus-mimicking nanomedicine eliminates cancer stem cells and mitigates chemoresistance in head and neck squamous cell carcinoma.Materials today. Bio · 2025Article
- Mechanistic insights into Y-Box binding protein-1 mediated regulation of lipid metabolism and oxidative stress in NAFLD via INHBE/TNF-β pathway.Biomolecules & biomedicine · 2025Article
- Targeting Epigenetic Dysregulations in Head and Neck Squamous Cell Carcinoma.Journal of dental research · 2025Review
- JMJD8 overexpression in breast cancer: implications for diagnosis, prognosis, and immune microenvironment interactions.Frontiers in oncology · 2025Article
- Molecular insight into histone methylation as a novel target for oral squamous cell carcinoma: future hope in personalised medicine.Journal of Cancer · 2025Review
- Context-dependent roles of mitochondrial LONP1 in orchestrating the balance between airway progenitor versus progeny cells.Cell stem cell · 2024Article
- Novel PROTAC probes targeting FOSL1 degradation to eliminate head and neck squamous cell carcinoma cancer stem cells.Bioorganic chemistry · 2024Article
- The expression of immune checkpoint proteins PD-L1 and TIM3 in mouse and human head and neck squamous cell carcinoma.European journal of oral sciences · 2024Article
- Oncogenic potential of SARS-CoV-2-targeting hallmarks of cancer pathways.Cell communication and signaling : CCS · 2024Review
- Histone-methyltransferase KMT2D deficiency impairs the Fanconi anemia/BRCA pathway upon glycolytic inhibition in squamous cell carcinoma.Nature communications · 2024Article
- The emerging roles of lysine-specific demethylase 4A in cancer: Implications in tumorigenesis and therapeutic opportunities.Genes & diseases · 2024Review
- Pharmacological inhibition of MYC to mitigate chemoresistance in preclinical models of squamous cell carcinoma.Theranostics · 2024Article
- CYTOR Facilitates Formation of FOSL1 Phase Separation and Super Enhancers to Drive Metastasis of Tumor Budding Cells in Head and Neck Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Androgen Receptor/AP-1 ActivatesCancers · 2023Article
- Carcinogenesis promotion in oral squamous cell carcinoma: KDM4A complex-mediated gene transcriptional suppression by LEF1.Cell death & disease · 2023Article
- JMJD8 Functions as a Novel AKT1 Lysine Demethylase.International journal of molecular sciences · 2022Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The transcription factor AP1 (activating protein 1), a heterodimer of the JUN and FOS proteins, promotes the invasive growth and metastasis of various tumors such as squamous cell carcinoma (SCC), breast cancer, and melanoma. AP1 activity is transcriptionally induced through a positive feedback loop. We identified the histone demethylase KDM4A (lysine-specific demethylase 4A) as a key epigenetic priming factor in this positive feedback loop. KDM4A contributed to the induction of genes encoding the AP1 transcription factors and the invasive growth and metastasis of SCC. KDM4A knockdown decreased the growth factor-induced messenger RNA expression and protein abundance of AP1 family members, including JUN and FOSL1. Mechanistically, histone demethylation by KDM4A facilitated the binding of the AP1 complex to the promoters of JUN and FOSL1, thereby promoting the positive feedback loop that maintains activation of AP1. In a mouse model of SCC, KDM4A knockdown inhibited lymph node metastasis. Moreover, the abundance of KDM4A correlated with the abundance of JUN and FOSL1 in human SCC tissues, and KDM4A expression was increased in human lymph node metastases. Our studies provide insights into the epigenetic control of AP1 and tumor invasion and suggest that KDM4A could be an important therapeutic target for inhibiting invasive SCC growth and metastasis.
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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.