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Endocan-PDGFRα mediated signaling drives glioblastoma spatial heterogeneity and influences tumor vasculature/radioresistance [ATAC-seq]

ABSTRACT: Endocan-PDGFRα mediated signaling drives glioblastoma spatial heterogeneity and influences tumor vasculature/radioresistance [ATAC-seq]

PROVIDER: PRJNA573085 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10156076.fastq.gz	Fastqsanger.gz
	SRR10156076_1.fastq.gz	Fastqsanger.gz
	SRR10156076_2.fastq.gz	Fastqsanger.gz
	SRR10156077.fastq.gz	Fastqsanger.gz
	SRR10156077_1.fastq.gz	Fastqsanger.gz

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Endocan-PDGFRα mediated signaling drives glioblastoma spatial heterogeneity and influences tumor vasculature/radioresistance

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Endocan-PDGFRα mediated signaling drives glioblastoma spatial heterogeneity and influences tumor vasculature/radioresistance [RNA-seq]

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Endocan-PDGFRα mediated signaling drives glioblastoma spatial heterogeneity and influences tumor vasculature/radioresistance

Project description:This SuperSeries is composed of the SubSeries listed below.

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Endocan-PDGFRα mediated signaling drives glioblastoma spatial heterogeneity and influences tumor vasculature/radioresistance [RNA-seq]

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Endocan-PDGFRα mediated signaling drives glioblastoma spatial heterogeneity and influences tumor vasculature/radioresistance [ATAC-seq]

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Endothelial-secreted Endocan protein activates PDGFRa signaling and regulates vascularity, radioresistance, and regional phenotype in glioblastoma

Project description:Extensive neovascularization is a hallmark of glioblastoma (GBM). In addition to supplying oxygen and nutrients, vascular endothelial cells provide trophic support to GBM cells via paracrine signaling. Here we report that Endocan (ESM1), an endothelial-secreted proteoglycan, confers enhanced proliferative, migratory, and angiogenic properties to GBM cells and regulates their spatial identity. Mechanistically, Endocan exerts at least part of its functions via direct binding and activation of the PDGFRA receptor. Subsequent downstream signaling enhances chromatin accessibility of the Myc promoter and upregulates Myc expression inducing stable phenotypic changes in GBM cells. Furthermore, Endocan confers a radioprotection phenotype in GBM cells, both in vitro and in vivo. Inhibition of Endocan-PDGFRA signaling with ponatinib increases survival in the Esm1 wild-type but not in the Esm1 knock-out mouse GBM model. Our findings identify Endocan and its downstream signaling axis as a potential target to subdue GBM recurrence and highlight the importance of vascular-tumor interactions for GBM development.

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Endothelial-secreted Endocan protein acts as a PDGFR alpha ligand and regulates vascularity, radioresistance, and regional phenotype in glioblastoma [2]

Project description:One of the hallmarks of glioblastoma (GBM) is extensive neovascularization. In addition to supplying blood and nutrients, vascular endothelial (VE) cells provide trophic support to GBM cells via paracrine signaling, the precise mechanisms of which are being unraveled. Here, using patient-derived GBM and VE cells as well as orthotopic GBM mouse models, we report that Endocan (ESM1), an endothelial-secreted proteoglycan, confers enhanced proliferative, migratory, and angiogenic properties to GBM cells and regulates their spatial identity. Mechanistically, Endocan exerts at least part of its functions via direct binding and activation of the PDGFRA receptor. Subsequent downstream signaling enhances chromatin accessibility of the Myc promoter and upregulates Myc expression inducing highly stable phenotypic changes in GBM cells. Furthermore, Endocan confers a radioprotection phenotype in GBM cells, both in vitro and in vivo. Inhibition of Endocan-PDGFRA signaling with ponatinib increases survival in the Esm1 wild-type but not in the Esm1 knock-out mouse GBM model. Our findings identify Endocan and its downstream signaling axis as a potential target to subdue the recurrence of GBM and further highlight the importance of vascular to tumor cell signaling for GBM biology.

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Endothelial-secreted Endocan protein acts as a PDGFR alpha ligand and regulates vascularity, radioresistance, and regional phenotype in glioblastoma [1]

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Endothelial-secreted Endocan protein acts as a PDGFR alpha ligand and regulates vascularity, radioresistance, and regional phenotype in glioblastoma

Project description:Endothelial-secreted Endocan protein acts as a PDGFR alpha ligand and regulates vascularity, radioresistance, and regional phenotype in glioblastoma

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Endothelial-secreted Endocan protein acts as a PDGFR alpha ligand and regulates vascularity, radioresistance, and regional phenotype in glioblastoma [1]

Project description:Endothelial-secreted Endocan protein acts as a PDGFR alpha ligand and regulates vascularity, radioresistance, and regional phenotype in glioblastoma [1]

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