ArticleOncotarget2015
Epigenetic reprogramming by tumor-derived EZH2 gain-of-function mutations promotes aggressive 3D cell morphologies and enhances melanoma tumor growth.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- A Real-World Disproportionality Analysis of FDA Adverse Event Reporting System Events for Tazemetostat.Therapeutic innovation & regulatory science · 2026Article
- Enhancer of zeste 2 polycomb repressive complex 2 subunit overexpression suppresses apoptosis in canine T-cell lymphoma: anFrontiers in veterinary science · 2026Article
- A Deep Learning-Based Model Approach for Quantitative Analysis of Cell Chemotaxis in a Microfluidic Chip.Sensors (Basel, Switzerland) · 2025Article
- Mining cancer genomes for change-of-metabolic-function mutations.Communications biology · 2023Article
- Integrative Multi-Omics Analysis of Oncogenic EZH2 Mutants: From Epigenetic Reprogramming to Molecular Signatures.International journal of molecular sciences · 2023Article
- Discovery of EEDi-5273 as an Exceptionally Potent and Orally Efficacious EED Inhibitor Capable of Achieving Complete and Persistent Tumor Regression.Journal of medicinal chemistry · 2021Article
- Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma.Journal of personalized medicine · 2021Review
- Epigenetic Silencing of CDR1as Drives IGF2BP3-Mediated Melanoma Invasion and Metastasis.Cancer cell · 2020Article
- The Emerging Roles of Heterochromatin in Cell Migration.Frontiers in cell and developmental biology · 2020Review
- The "ART" of Epigenetics in Melanoma: From histone "Alterations, to Resistance and Therapies".Theranostics · 2020Review
- Discovery of selective activators of PRC2 mutant EED-I363M.Scientific reports · 2019Article
- Dissecting the role of H3K27 acetylation and methylation in PRC2 mediated control of cellular identity.Nature communications · 2019Article
- Epigenetic Enzyme Mutations: Role in Tumorigenesis and Molecular Inhibitors.Frontiers in oncology · 2019Review
- Tackling malignant melanoma epigenetically: histone lysine methylation.Clinical epigenetics · 2018Review
- SIRT6 haploinsufficiency induces BRAFNature communications · 2018Article
- Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target.The Journal of pathology · 2018Article
- Histone modifiers: Dynamic regulators of the cutaneous transcriptome.Journal of dermatological science · 2018Review
- Orchestration of H3K27 methylation: mechanisms and therapeutic implication.Cellular and molecular life sciences : CMLS · 2018Review
- Identification of coexistence of BRAF V600E mutation and EZH2 gain specifically in melanoma as a promising target for combination therapy.Journal of translational medicine · 2017Article
- A new transgenic mouse model for conditional overexpression of the Polycomb Group protein EZH2.Transgenic research · 2017Article
Corrections and comments
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In addition to genetic alterations, cancer cells are characterized by myriad epigenetic changes. EZH2 is a histone methyltransferase that is over-expressed and mutated in cancer. The EZH2 gain-of-function (GOF) mutations first identified in lymphomas have recently been reported in melanoma (~2%) but remain uncharacterized. We expressed multiple EZH2 GOF mutations in the A375 metastatic skin melanoma cell line and observed both increased H3K27me3 and dramatic changes in 3D culture morphology. In these cells, prominent morphological changes were accompanied by a decrease in cell contractility and an increase in collective cell migration. At the molecular level, we observed significant alteration of the axonal guidance pathway, a pathway intricately involved in the regulation of cell shape and motility. Furthermore, the aggressive 3D morphology of EZH2 GOF-expressing melanoma cells (both endogenous and ectopic) was attenuated by EZH2 catalytic inhibition. Finally, A375 cells expressing exogenous EZH2 GOF mutants formed larger tumors than control cells in mouse xenograft studies. This study not only demonstrates the first functional characterization of EZH2 GOF mutants in non-hematopoietic cells, but also provides a rationale for EZH2 catalytic inhibition in melanoma.
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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.