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Endothelial Pim3 kinase protects the vascular barrier during lung metastasis (set2)

ABSTRACT: Endothelial Pim3 kinase protects the vascular barrier during lung metastasis (set2)

PROVIDER: PRJNA1066871 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27658009.fastq.gz	Fastqsanger.gz
	SRR27658010.fastq.gz	Fastqsanger.gz
	SRR27658011.fastq.gz	Fastqsanger.gz
	SRR27658012.fastq.gz	Fastqsanger.gz
	SRR27658013.fastq.gz	Fastqsanger.gz

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Endothelial Pim3 kinase protects the vascular barrier during lung metastasis (set2)

Project description:Endothelial cells (ECs) form a tissue-specific barrier for disseminating cancer cells in distant organs. However, the molecular regulation of the ECs in the metastatic niche is poorly understood. Here, we analyzed the transcriptional reprogramming of ECs in the lung metastatic niche six hours after the arrival of melanoma cells in the niche. We discovered a novel EC cluster derived from venous capillaries in response to infiltrating cancer cells, which was enriched for cell-cell communication pathways, including the Dll4, Vegf and Il6-Jak-Stat pathways. The Jak-Stat activated oncogenic Pim3 kinase was a marker of the cancer responding ECs, being upregulated in spontaneous metastasis models and in ECs of human cancer. Notably, PIM inhibition increased vascular leakage and metastatic colonization in vivo and impaired the EC barrier via decreased junctional Cadherin-5 and catenins a, b and d. Thus, PIM3 protects the EC barrier in the metastatic niche, which may impair the efficacy of PIM inhibitors in cancer therapies.

2024-09-20 | GSE253749 | GEO

Endothelial Pim3 kinase protects the vascular barrier during lung metastasis

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Endothelial Pim3 kinase protects the vascular barrier during lung metastasis (set3)

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Endothelial Pim3 kinase protects the vascular barrier during lung metastasis

Project description:Endothelial Pim3 kinase protects the vascular barrier during lung metastasis

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Endothelial Pim3 kinase protects the vascular barrier during lung metastasis

Project description:Endothelial Pim3 kinase protects the vascular barrier during lung metastasis

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Endothelial Pim3 kinase protects the vascular barrier during lung metastasis (set3)

Project description:Endothelial Pim3 kinase protects the vascular barrier during lung metastasis (set3)

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Endothelial Pim3 kinase protects the vascular barrier during lung metastasis

Project description:To investigate transcriptome changes of endothelial cells during cancer cell response, we studied HUVEC RNA expression in conditioned medium derived from empty plates versus B16-F10 melanoma cultures.

2024-09-11 | GSE251979 | GEO

CRISPR/Cas9-mediated knockout of PIM3 suppresses tumorigenesis and cancer cell stemness in human hepatoblastoma cells.

Project description:Hepatoblastoma remains one of the most difficult childhood tumors to treat and is alarmingly understudied. Over half of patients initially present with locally advanced or metastatic disease and the prognosis for this cohort remains dismal. In addition, many of these children have disease that is resistant to standard therapies and will require novel and targeted therapies to effectively treat or manage their disease. We previously demonstrated that Proviral Insertion site in Maloney murine leukemia virus (PIM) kinases, specifically PIM3, are overexpressed in human hepatoblastoma cells and function to promote tumorigenesis. We aimed to use CRISPR/Cas9 gene editing technology with dual gRNAs to introduce large inactivating deletions in the PIM3 gene and achieve stable PIM3 knockout (KO) in the human hepatoblastoma cell line, HuH6. PIM3 KO of hepatoblastoma cells led to significantly decreased proliferation, viability, and motility, inhibited cell-cycle progression, decreased tumor growth in a xenograft murine model, and increased animal survival. Analysis of RNA sequencing data revealed that PIM3 KO downregulated expression of pro-migratory and pro-invasive genes and upregulated expression of genes involved in apoptosis and differentiation. Furthermore, PIM3 KO decreased hepatoblastoma cancer cell stemness as evidenced by decreased tumorsphere formation, decreased mRNA abundance of stemness markers, and decreased cell surface expression of CD133, a marker of hepatoblastoma stem cell-like cancer cells. Reintroduction of PIM3 into PIM3 KO cells rescued the malignant phenotype. These findings emphasize the role of PIM3 in promoting hepatoblastoma tumorigenesis and provide evidence that targeting PIM3 may offer a novel therapeutic approach for children with hepatoblastoma.

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2012-07-25 | GSE28098 | GEO

Neutralization of truncated procalcitonin by antibody treatment protects vascular barrier integrity during systemic inflammation

Project description:Neutralization of truncated procalcitonin by antibody treatment protects vascular barrier integrity during systemic inflammation

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