Aberrant Activation of β-Catenin Signaling Drives Glioma Tumorigenesis via USP1-Mediated Stabilization of EZH2

Ma, Li; Lin, Kangyu; Chang, Guoqiang; Chen, Yiwen; Chen, Yue; Guo, Qing; Zhang, Sicong; Jia, Zhiliang; Huang, Tony T.; Zhou, Aidong; Huang, Suyun

doi:10.1158/0008-5472.can-18-1304

Cited by 49 publications

(30 citation statements)

References 42 publications

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“…comes from studies linking EZH2 to b-catenin [53,54]. For example, in glioma cells b-catenin signaling can increase and stabilize EZH2 activity by activating the USP1 deubiquitinase involved in its degradation in vitro [55]. Hence, EZH2 may activate the b-catenin pathway, thereby potentially contributing to a noninflamed state in melanoma cells [56].…”

Section: Drivers Of Dna Methylation: Putative Role Of Suppressive Prcmentioning

confidence: 99%

“…For example, in glioma cells b-catenin signaling can increase and stabilize EZH2 activity by activating the USP1 deubiquitinase involved in its degradation in vitro [55]. Hence, EZH2 may activate the b-catenin pathway, thereby potentially contributing to a noninflamed state in melanoma cells [56]. Other precedents for this hypothesis include the observation in a murine liver cancer model that liver cancerinitiating cells (TICs) could be renewed on EZH2-dependent activation of the Wnt/b-catenin pathway; by contrast, an EZH2 inhibitor could deplete liver TICs in this model [57].…”

Section: Drivers Of Dna Methylation: Putative Role Of Suppressive Prcmentioning

confidence: 99%

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Targeting DNA Methylation and EZH2 Activity to Overcome Melanoma Resistance to Immunotherapy

Emran

Chatterjee

Rodger

et al. 2019

Trends in Immunology

169

137

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Methylation of DNA at CpG sites is the most common and stable of epigenetic changes in cancer. Hypermethylation acts to limit immune checkpoint blockade immunotherapy by inhibiting endogenous interferon responses needed for recognition of cancer cells. By contrast, global hypomethylation results in the expression of programmed death ligand 1 (PD-L1) and inhibitory cytokines, accompanied by epithelial-mesenchymal changes that can contribute to immunosuppression. The drivers of these contrasting methylation states are not well understood. DNA methylation also plays a key role in cytotoxic T cell 'exhaustion' associated with tumor progression. We present an updated exploratory analysis of how DNA methylation may define patient subgroups and can be targeted to develop tailored treatment combinations to help improve patient outcomes. DNA Methylation, ICB, and Cancer DNA methylation can have major effects on gene expression and is the most commonly studied type of epigenetic modification (see Glossary). It comprises the covalent modification of the nucleotide cytosine at the 5ʹ position at sites preceding guanine (CpG) [1]. During mammalian cell division, it is replicated by the maintenance enzyme DNA methyltransferase 1 (DNMT1) on the daughter strand cytosine at the complementary CpG, usually resulting in gene silencing. New sites of DNA methylation, known as de novo methylation, can be introduced by DNMT3a or DNMT3b (Box 1). Conversely, methyl groups can be erased by ten-eleven translocation (TET) family proteins followed by glycosylation and replacement with an unmethylated cytosine. DNMT1 recruitment to replicating chromatin is facilitated by the 'ubiquitin-like with PHD and ring-finger domains' (UHRF) E3 ubiquitin ligase UHRF1 [2,3]. Methylation at CpG sites can also be recognized by methyl CpG binding 'reader' proteins such as methyl-CpG binding domain protein 1 (MBD1) and methyl-CpG binding protein 2 (MeCP2) harboring transcriptionally repressive activity. The latter may bind histone deacetylases (HDACs), which can contribute to the repression of certain genes [4]. Highlights Genome-wide DNA methylation is a relatively stable epigenetic characteristic of cells, which can be dysregulated in cancer cells by oncogenic signals.

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Section: Drivers Of Dna Methylation: Putative Role Of Suppressive Prcmentioning

confidence: 99%

Section: Drivers Of Dna Methylation: Putative Role Of Suppressive Prcmentioning

confidence: 99%

Targeting DNA Methylation and EZH2 Activity to Overcome Melanoma Resistance to Immunotherapy

Emran

Chatterjee

Rodger

et al. 2019

Trends in Immunology

169

137

View full text Add to dashboard Cite

show abstract

“…IHC analysis was conducted as described elsewhere. 22 The IHC staining results were evaluated by two independent pathologists (double-blinded). Briefly, the percentage of stained tumour cells (0, 0-5%; 1, 6-25%; 2, 26-50%; 3, 50%-100%) and staining intensity scores (0, negative; 1, weak; 2, moderate; 3, strong) were summed.…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

PLAGL2 promotes epithelial–mesenchymal transition and mediates colorectal cancer metastasis via β-catenin-dependent regulation of ZEB1

Zhou

Han

et al. 2019

Br J Cancer

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BACKGROUND: We previously demonstrated that the pleomorphic adenoma gene like-2 (PLAGL2) is involved in the pathogenesis of Hirschsprung disease. Enhanced PLAGL2 expression was observed in several malignant tumours. However, the exact function of PLAGL2 and its underlying mechanism in colorectal cancer (CRC) remain largely unknown. METHODS: Immunohistochemical analysis of PLAGL2 was performed. A series of in vitro and in vivo experiments were conducted to reveal the role of PLAGL2 in the progression of CRC. RESULTS: Enhanced PLAGL2 expression was significantly associated with EMT-related proteins in CRC. The data revealed that PLAGL2 promotes CRC cell proliferation, migration, invasion and EMT both in vitro and in vivo. Mechanistically, PLAGL2 promoted the expression of ZEB1. PLAGL2 enhanced the expression and nuclear translocation of β-catenin by decreasing its phosphorylation. The depletion of β-catenin neutralised the regulation of ZEB1 that was caused by enhanced PLAGL2 expression. The small-molecule inhibitor PNU-74654, also impaired the enhancement of ZEB1 that resulted from the modified PLAGL2 expression. The depletion of ZEB1 could block the biological function of PLAGL2 in CRC cells. CONCLUSIONS: Collectively, our findings suggest that PLAGL2 mediates EMT to promote colorectal cancer metastasis via βcatenin-dependent regulation of ZEB1.

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“…23,24 Recent research has indicated that polycomb group members, such as EZH2, Bmi1, KDM2B, PHF19, SUZ12, CBX8, and so on, are involved in the proliferation of cancer cell including glioma cells. 20,[25][26][27][28][29][30][31] In the present study, we revealed the association between PCGF1 and various characteristics of glioblastoma (GBM).…”

Section: Discussionmentioning

confidence: 73%

<p>Repression of PCGF1 Decreases the Proliferation of Glioblastoma Cells in Association with Inactivation of c-Myc Signaling Pathway</p>

Yan¹,

Cui²,

Dong³

et al. 2020

OTT

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Glioblastoma (GBM) is the most common primary brain tumor with a poor therapeutic outcome. Polycomb group factor 1 (PCGF1), a member of the PcG (Polycomb group) family, is highly expressed in the developing nervous system of mice. However, the function and the mechanism of PCGF1 in GBM proliferation still remain unclear. Methods: Knockdown of PCGF1 was performed in U87 GBM cell by shRNA strategy via lentivirus vector. MTT assay, colony formation assays, and flow cytometry were used to measure the properties of cell proliferation and cell cycle distribution, respectively. GeneChip analysis was performed to identify the downstream effector molecules. Rescue assay was constructed to verify the screening results. Results: We first found that knockdown of PCGF1 led to the inhibition of U87 cells proliferation and decreased colony formation ability. The data from GeneChip expression profiling and Ingenuity Pathway Analysis (IPA) indicated that many of the altered gene cells are associated with the cell proliferation control pathways. We have further confirmed the suppression of AKT/ GSK3β/c-Myc/cyclinD1 expressions by Western blotting analysis. The over-expression of c-Myc could partly restore the attenuated proliferation ability caused by knockdown of PCGF1. Conclusion: All the above evidences suggested that PCGF1 might be closely associated with tumorigenesis and progression of glioblastoma (GBM), in which process the oncoprotein c-Myc may participate. PCGF1 could thus be a potential therapeutic target for the treatment of glioblastoma (GBM).

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Aberrant Activation of β-Catenin Signaling Drives Glioma Tumorigenesis via USP1-Mediated Stabilization of EZH2

Cited by 49 publications

References 42 publications

Targeting DNA Methylation and EZH2 Activity to Overcome Melanoma Resistance to Immunotherapy

Targeting DNA Methylation and EZH2 Activity to Overcome Melanoma Resistance to Immunotherapy

PLAGL2 promotes epithelial–mesenchymal transition and mediates colorectal cancer metastasis via β-catenin-dependent regulation of ZEB1

<p>Repression of PCGF1 Decreases the Proliferation of Glioblastoma Cells in Association with Inactivation of c-Myc Signaling Pathway</p>

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