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JAGGED1 Promotes Tumor Progression through Recruitment of Macrophages and Functional Suppression of Tumor-killing T cells

ABSTRACT: JAGGED1 Promotes Tumor Progression through Recruitment of Macrophages and Functional Suppression of Tumor-killing T cells

PROVIDER: PRJNA679314 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13082214_1.fastq.gz	Fastqsanger.gz
	SRR13082214_2.fastq.gz	Fastqsanger.gz
	SRR13082215_1.fastq.gz	Fastqsanger.gz
	SRR13082215_2.fastq.gz	Fastqsanger.gz
	SRR13082216_1.fastq.gz	Fastqsanger.gz

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JAGGED1 Promotes Tumor Progression through Recruitment of Macrophages and Functional Suppression of Tumor-killing T cells [scRNA-seq]

Project description:Breast cancer is one of the leading causes of cancer-related mortality in women. NOTCH signaling is a well conserved pathway which not only plays critical roles in normal development, but also in cancer progression. One of the Notch ligand, JAGGED1 is overexpressed in about 30% of breast cancer patients. However, the role of JAGGED1 in breast tumorigenesis has not been rigorously examined. By utilizing genetic engineered mouse models of mammary specific Jagged1 expression or knockout, we discover that Jagged1 promotes tumorigenesis in multiple spontaneous mammary tumor models. Jagged1 expression leads to increased infiltration of tumor associated macrophages and decreased presentation of T cells within tumor microenvironment. Depletion of macrophages or T cells by neutralizing antibodies diminishes the tumor-promoting effect caused by Jagged1. Mechanistically, Jagged1 activates Notch signaling in tumor cells, leads to increased expression and secretion of multiple cytokines, including IL-6 and WISP. These cytokines help recruit macrophages into the tumor microenvironment. Macrophages crosstalk with infiltrated T cells and inhibit their cytotoxic killing on tumor cells. In triple negative breast cancer patient samples, high expression level of JAGGED1 correlates with increased macrophage infiltration and decreased T cell infiltration within tumor tissues. JAGGED1 also promotes tumor progression in several other solid cancer types, including melanoma, and colon cancer in a T cell dependent manner. Co-administration of immune checkpoint inhibitor, PD-1 antibody with gamma-secretase inhibitor (GSI) significantly inhibits tumor growth. These findings identify a unique oncogenic crosstalk between tumor derived JAGGED1, Macrophages, and T cells to promote tumor progression.

2022-03-08 | GSE161769 | GEO

JAGGED1 Promotes Tumor Progression through Recruitment of Macrophages and Functional Suppression of Tumor-killing T cells [RNA-seq]

2022-03-08 | GSE161768 | GEO

JAGGED1 Promotes Tumor Progression through Recruitment of Macrophages and Functional Suppression of Tumor-killing T cells [RNA-seq]

Project description:JAGGED1 Promotes Tumor Progression through Recruitment of Macrophages and Functional Suppression of Tumor-killing T cells [RNA-seq]

| PRJNA679319 | ENA

JAGGED1 Promotes Tumor Progression through Recruitment of Macrophages and Functional Suppression of Tumor-killing T cells [scRNA-seq]

Project description:JAGGED1 Promotes Tumor Progression through Recruitment of Macrophages and Functional Suppression of Tumor-killing T cells [scRNA-seq]

| PRJNA679322 | ENA

Tumor-derived Jagged1- and Notch-dependent transcription changes in MC3T3-E1 osteoblasts

Project description:Transcriptional profiling of MC3T3-E1 osteoblasts that were flow cytometry-separated from cocultures with control or Jagged1-overexpressing tumor cells and treated with either DMSO control or 1μM MRK-003 (gamma-secretase inhibitor). One cell line (MC3T3-E1) cells: four different experimental conditions: cultured with (1) control tumor cells + DMSO; (2) Jagged1-overexpressing tumor cells + DMSO; (3) control tumor cells + MRK-003; (4) Jagged1-overexpressing tumor cells + MRK-003. Each experiment has two biological replicates. Total, 8 samples.

2010-08-15 | E-GEOD-20517 | biostudies-arrayexpress

JAGGED1 Promotes Tumor Progression through Recruitment of Macrophages and Functional Suppression of Tumor-killing T cells

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

2022-03-08 | GSE161770 | GEO

Genes regulated/modulated by jagged1 in endothelial cells during inflammation

Project description:Proinflammatory activation of endothelial cells leads to recruitment of leukocytes by upregulation of adhesion molecules and presentation of chemoattractants. In response to such activation there is also a strong shift in the endothelial expression of Notch ligands, with downregulation of Dll4 and a upregulation of JAG1. To assess whether Jagged1 would affect the endothelial activation profile, we suppressed JAG1 expression during IL-1β-induced activation by means of siRNA and performed a genome-wide transcriptome analysis. Our results show for the first time that Jagged1 modulates the transcription profile of activated endothelial cells and describe data that imply a role for Jagged1 in sharpening the inflammatory profile of the vasculature, giving it an edge towards leukocyte recruitment. These findings imply that Jagged1 might be a potential therapeutic target to attenuate inflammation and reduce tissue damage in inflammatory diseases.

2018-08-29 | GSE39180 | GEO

Tumor-derived Jagged1- and Notch-dependent transcription changes in MC3T3-E1 osteoblasts

2010-08-15 | GSE20517 | GEO

Jagged1 regulates miRNA expression profile

Project description:miRNA expression profiles of HMECs treated with 40mM Jagged1 (JAG1) or the control peptide for 1 day Genome-wide miRNA PCR array analysis was performed using human miRNA PCR arrays (MIHS216Z, SABiosceinces) acccording to the manufacturer's instructions

2014-05-30 | E-GEOD-56801 | biostudies-arrayexpress