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Blocking immunosuppressive neutrophils deters pY696-EZH2-driven brain metastases

ABSTRACT: In brain metastatic cells, enhancer of zeste homologue 2 (EZH2) is highly expressed and phosphorylated at tyrosine-696 (pY696-EZH2) by nuclear-localized Src tyrosine kinase. Phosphorylation of EZH2 at Y696 changes its binding preference from histone H3 to RNA polymerase II, which consequently switches EZH2’s function from a methyltransferase to a transcription factor that increases c-Jun expression. c-Jun upregulates pro-tumorigenic inflammatory cytokines, including granulocyte-colony stimulating factor (G-CSF), which recruits Arg1-positive and PD-L1-positive immunosuppressive neutrophils into the brain to drive metastasis outgrowth.

ORGANISM(S): Homo sapiens

PROVIDER: GSE188640 | GEO | 2021/11/14

REPOSITORIES: GEO

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Blocking immunosuppressive neutrophils deters pY696-EZH2-driven brain metastases

Project description:Blocking immunosuppressive neutrophils deters pY696-EZH2-driven brain metastases

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RNAi profiling of human ezh2 specific siRNA A673 treated cells reveals EZh2 is a mediator of EWS-FLI1 driven tumor growth blocking endothelial and neuro-ectodermal differentiation

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