2020
DOI: 10.1186/s12943-020-01173-x
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Verification of EZH2 as a druggable target in metastatic uveal melanoma

Abstract: Background: Hepatic 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… Show more

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Cited by 44 publications
(33 citation statements)
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“…The proportion of CSC was increased through miR-29c-DVL2-β-catenin signal pathway, and migration and invasion were promoted through RhoGDI γ-rac1 axis. 11 A similar conclusion has been reached in CM-CSC study. 44 JARID1B is a lysine-specific demethylase, which belongs to the JmjC domain protein family.…”
Section: Dovepresssupporting
confidence: 80%
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“…The proportion of CSC was increased through miR-29c-DVL2-β-catenin signal pathway, and migration and invasion were promoted through RhoGDI γ-rac1 axis. 11 A similar conclusion has been reached in CM-CSC study. 44 JARID1B is a lysine-specific demethylase, which belongs to the JmjC domain protein family.…”
Section: Dovepresssupporting
confidence: 80%
“…34 In UM cell line OMM1, ALDH+ cells can form more subcutaneous xenografted tumors in NOD/SCID mice than ALDH-cells, which proves that ALDH+ cell subsets can enrich more CSC in UM. 11 Several studies on targeted therapy of CM with ALDH isozyme have made good progress, which provides evidence for the treatment of CSC in the future. 35,36 SOX2, a member of the transcription factor family of embryonic stem cells, is expressed in the nucleus and plays a key role in the development of embryonic stem cells and in maintaining the pluripotency and self-renewal of embryonic stem cells and some cell lines (such as nerve cells, osteoblasts and melanocytes derived from neural crest).…”
Section: Dovepressmentioning
confidence: 96%
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“…UM resists most current treatments [ 27 , 28 ] with half of the cases [ 29 ] eventually resulting in liver metastasis and poor prognosis. It would therefore be ideal if preventative measures can be identified to reduce the risk of developing UM altogether, just as sun-avoidance initiatives have improved the burden of CM in the younger generations [ 15 ].…”
Section: Introductionmentioning
confidence: 99%
“…Previous studies have proven that EZH2, which mediates the tri-methylation of H3K27 and is related to gene silencing, is an important oncogenic driver and may play a potential therapeutic role in human cancers. [33][34][35] Recently, relevant studies have identified a tight relationship between NSD2 and EZH2. The EZH2-NSD2-HMTase axis is coordinated by a microRNA network, which is regulated via microRNA miR-31, miR-26a, and miR-203.…”
Section: Nsd2 Regulates the Process Of Emtmentioning
confidence: 99%