ArticleMolecular cancer2020
Verification of EZH2 as a druggable target in metastatic uveal melanoma.
Article in Molecular cancer, 2020. 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, 52 citations in OpenAlex.
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- Data-driven strategies for immunoradiotherapy in uveal melanoma: the role of artificial intelligence.Frontiers in pharmacology · 2026Review
- Identification of Nogo-B as a potential therapeutic target of osteosarcoma via stereochemically selective covalent probes.Cell death & disease · 2025Article
- Effects of solamargine in hepatic metastasis of colorectal cancer: induction of ferroptosis and elimination of cancer stem cells.Chinese medicine · 2025Article
- An overview of BAP1 biological functions and current therapeutics.Biochimica et biophysica acta. Reviews on cancer · 2025Review
- Research Progress on the Role of Ubiquitination in Eye Diseases.Cell biochemistry and biophysics · 2024Review
- Targeting the chromatin structural changes of antitumor immunity.Journal of pharmaceutical analysis · 2024Review
- EHMT2 promotes tumorigenesis inActa pharmaceutica Sinica. B · 2024Article
- Mass Spectrometry-Based Profiling of Histone Post-Translational Modifications in Uveal Melanoma Tissues, Human Melanocytes, and Uveal Melanoma Cell Lines - A Pilot Study.Investigative ophthalmology & visual science · 2024Article
- Multi-omics approaches identify novel prognostic biomarkers of autophagy in uveal melanoma.Journal of cancer research and clinical oncology · 2023Article
- Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2).Journal of medicinal chemistry · 2023Review
- FGF-trapping hampers cancer stem-like cells in uveal melanoma.Cancer cell international · 2023Article
- Novel insights into histone lysine methyltransferases in cancer therapy: From epigenetic regulation to selective drugs.Journal of pharmaceutical analysis · 2023Review
- Epigenetic drug library screening reveals targeting DOT1L abrogates NADJournal of pharmaceutical analysis · 2023Article
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- BAP1 in cancer: epigenetic stability and genome integrity.Discover oncology · 2022Review
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- The role of epigenetic modifications in Colorectal Cancer Metastasis.Clinical & experimental metastasis · 2022Review
- Molecular mechanisms and clinical applications of exosomes in prostate cancer.Biomarker research · 2022Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatic metastasis develops in ~ 50% of uveal melanoma (UM) patients with no effective treatments. Although GNAQ/GNA11 mutations are believed to confer pathogenesis of UM, the underlying mechanism of liver metastasis remains poorly understood. Given that profound epigenetic evolution may occur in the long journey of circulating tumor cells (CTCs) to distant organs, we hypothesized that EZH2 endowed tumor cells with enhanced malignant features (e.g., stemness and motility) during hepatic metastasis in UM. We aimed to test this hypothesis and explore whether EZH2 was a therapeutic target for hepatic metastatic UM patients.
methodsExpression of EZH2 in UM was detected by qRT-PCR, Western blotting and immunohistochemistry staining. Proliferation, apoptosis, cancer stem-like cells (CSCs) properties, migration and invasion were evaluated under circumstances of treatment with either EZH2 shRNA or EZH2 inhibitor GSK126. Antitumor activity and frequency of CSCs were determined by xenografted and PDX models with NOD/SCID mice. Hepatic metastasis was evaluated with NOG mice.
resultsWe found that EZH2 overexpressed in UM promoted the growth of UM; EZH2 increased the percentage and self-renewal of CSCs by miR-29c-DVL2-β-catenin signaling; EZH2 facilitates migration and invasion of UM cells via RhoGDIγ-Rac1 axis. Targeting EZH2 either by genetics or small molecule inhibitor GSK126 decreased CSCs and motility and abrogated the liver metastasis of UM.
conclusionsThese findings validate EZH2 as a druggable target in metastatic UM patients, and may shed light on the understanding and interfering the complicated metastatic process.
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