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Transcriptome analysis of J558 allograft mouse model treated with the CDC7-specific inhibitor TAK-931 [RNA-seq]

ABSTRACT: Transcriptome analysis of J558 allograft mouse model treated with the CDC7-specific inhibitor TAK-931 [RNA-seq]

PROVIDER: PRJNA1026573 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26340437_1.fastq.gz	Fastqsanger.gz
	SRR26340437_2.fastq.gz	Fastqsanger.gz
	SRR26340438_1.fastq.gz	Fastqsanger.gz
	SRR26340438_2.fastq.gz	Fastqsanger.gz
	SRR26340439_1.fastq.gz	Fastqsanger.gz

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Transcriptome analysis of J558 allograft mouse model treated with the CDC7-specific inhibitor TAK-931 [RNA-seq]

Project description:To comprehensively evaluate in vivo inflammatory effects of TAK-931 in tumor microenvironment, RNA-seq was conducted in the J558 allograft mouse model. The GSEA revealed significant enrichment of inflammatory hallmarks in TAK-931-treated allografts. Metascape analyses also visualized that the network modules of the inflammatory signaling pathways were predominantly enriched.

2023-11-05 | GSE244988 | GEO

Gene expression profile at single cell level of J558 allograft mouse model treated with the CDC7-specific inhibitor TAK-931 [scRNA-seq]

Project description:To comprehensively evaluate in vivo inflammatory effects of TAK-931 in tumor microenvironment, scRNA-seq was conducted in the J558 allograft mouse model. The tSNE plots and the expression dot plots showed cellular components in the allografts classified by the indicated TME markers: cancer cell (J558 allograft), monocyte, CD8+ T cell, CD4+ T cell, NK cell, endothelial cell, fibroblast, and undefined, demonstrating that TAK-931 treatment prominently promoted tumor infiltration of both adaptive (CD8+ T cell and CD4+ T cell) and innate (NK cells and monocytes) immune cells in the allografts.

2023-11-05 | GSE244986 | GEO

Gene expression profile at single cell level of HeLa cells treated with the CDC7-specific inhibitor TAK-931 [scRNA-seq]

Project description:We performed scRNA-seq analyses to determine the transcriptional landscape of the TAK-931-induced aneuploid cells at the single-cell levels. HeLa cells were treated with DMSO or TAK-931 (300 nM) for 72 h. In the t-SNE plots, the DMSO- and TAK-931-treated cells were classified in two distinct clusters. Indicating that the major population of the TAK-931-treated aneuploid HeLa cells was transformed to a cell contexture that was transcriptionally distinct from that of DMSO-treated control cells. The hallmark of an inflammatory response was remarkably enriched in the TAK-931 treatment cluster. In addition, the positive cells of inflammatory cytokine/chemokine-related genes, such as CXCL8, IL1B, TNHSF14 and TNFRSF1B, were significantly accumulated in the TAK-931-treatment cluster.

2023-11-05 | GSE244987 | GEO

Transcriptome analysis of HeLa cells treated with the CDC7-specific inhibitor TAK-931 [RNA-seq]

Project description:The results showed that 48-h treatment upregulated 138 genes and 72-h treatment upregulated 504 genes. In the Metascape analyses, the TNF signaling pathway was a dominant network module in the 48-h treatment group, while the inflammatory-related modules were more intensively accumulated, and the signaling networks expanded to the surrounding various modules in the 72-h treatment. Our signaling module results indicate that the TAK-931-induced cellular senescence progressed in a time-dependent manner, and mTOR pathways plays important roles in viability for TAK-931-induced senescent cells.

2023-11-05 | GSE245063 | GEO

Transcriptome analysis of HeLa cells treated with the CDC7-specific inhibitor TAK-931 [RNA-seq]

Project description:Transcriptome analysis of HeLa cells treated with the CDC7-specific inhibitor TAK-931 [RNA-seq]

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Gene expression profile at single cell level of J558 allograft mouse model treated with the CDC7-specific inhibitor TAK-931 [scRNA-seq]

Project description:Gene expression profile at single cell level of J558 allograft mouse model treated with the CDC7-specific inhibitor TAK-931 [scRNA-seq]

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Gene expression profile at single cell level of HeLa cells treated with the CDC7-specific inhibitor TAK-931 [scRNA-seq]

Project description:Gene expression profile at single cell level of HeLa cells treated with the CDC7-specific inhibitor TAK-931 [scRNA-seq]

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RNA-seq of human breast epithelial cell line MCF10A treated for 8 days with the CDC7 inhibitors XL413, TAK-931 against DMSO-treated controls

Project description:CDC7 is a serine-threonine kinase, which has an important role in the activation of replication origins in the S-phase. CDC7 is also a potential molecular target for the development of anticancer drugs. Multiple studies have shown that different cell lines have a wide range of sensitivity to CDC7 inhibition. However, how the manner in which cells respond to prolonged CDC7 inhibition has yet to be investigated. Hence, we performed an RNA-sequencing experiment to investigate variation in gene expression in cells undergoing prolonged CDC7 inhibition.

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Molecular mechanism and potential target indication of TAK-931, a novel CDC7-selective inhibitor.

Project description:Replication stress (RS) is a cancer hallmark; chemotherapeutic drugs targeting RS are widely used as treatments for various cancers. To develop next-generation RS-inducing anticancer drugs, cell division cycle 7 (CDC7) has recently attracted attention as a target. We have developed an oral CDC7-selective inhibitor, TAK-931, as a candidate clinical anticancer drug. TAK-931 induced S phase delay and RS. TAK-931-induced RS caused mitotic aberrations through centrosome dysregulation and chromosome missegregation, resulting in irreversible antiproliferative effects in cancer cells. TAK-931 exhibited significant antiproliferative activity in preclinical animal models. Furthermore, in indication-seeking studies using large-scale cell panel data, TAK-931 exhibited higher antiproliferative activities in RAS-mutant versus RAS-wild-type cells; this finding was confirmed in pancreatic patient-derived xenografts. Comparison analysis of cell panel data also demonstrated a unique efficacy spectrum for TAK-931 compared with currently used chemotherapeutic drugs. Our findings help to elucidate the molecular mechanisms for TAK-931 and identify potential target indications.

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A Study to Evaluate the Safety, Tolerability, and Activity of TAK-931 in Participants With Metastatic Pancreatic Cancer, Metastatic Colorectal Cancer, and Other Advanced Solid Tumors

Project description:The purpose of this study is to confirm the safety and tolerability of TAK-931 in a cohort of Western participants with metastatic solid tumors and to evaluate the anti-tumor activity of TAK-931 in participants with metastatic pancreatic cancer, colorectal cancer (CRC), squamous esophageal cancer (sqEC), and squamous non-small-cell lung cancer (sqNSCLC).

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