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HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway via stimulating MSK1 kinase and suppressing PPP2R2B protein

ABSTRACT: HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway via stimulating MSK1 kinase and suppressing PPP2R2B protein

PROVIDER: PRJNA612479 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11305671.fastq.gz	Fastqsanger.gz
	SRR11305672.fastq.gz	Fastqsanger.gz
	SRR11305673.fastq.gz	Fastqsanger.gz
	SRR11305674.fastq.gz	Fastqsanger.gz
	SRR11305675.fastq.gz	Fastqsanger.gz

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HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway via stimulating MSK1 kinase and suppressing PPP2R2B protein

Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, which lacks effective therapies. Here, we demonstrate that the transcription factor, HOXC6, is overexpressed in most PDACs, and its inhibition blocks PDAC tumor growth and metastasis. HOXC6 transcriptionally activates tumor-promoting kinase MSK1 and suppresses tumor-inhibitory protein PPP2R2B in PDAC. HOXC6-induced PPP2R2B suppression causes mTOR pathway activation, which facilitates PDAC growth. Also, MSK1 upregulation by HOXC6 is necessary for PDAC growth due to its ability to suppress apoptosis via its substrate DDX17. Combinatorial pharmacological inhibition of MSK1 and mTOR potently suppressed PDAC tumor growth and metastasis in PDAC mouse models. PDAC cells with acquired resistance to MSK1/mTOR-inhibitors displayed activated IGF1R signaling and were successfully eradicated by IGF1R inhibitor. Furthermore, MEK inhibitor trametinib enhanced the efficacy of dual MSK1 and mTOR inhibition. Collectively, these results identify therapeutic vulnerabilities of PDAC and an approach to overcome acquired drug resistance to prolong therapeutic benefit.

2023-10-30 | GSE150222 | GEO

HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway via stimulating MSK1 kinase and suppressing PPP2R2B protein

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HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway via stimulating MSK1 kinase and suppressing PPP2R2B protein

2023-10-30 | GSE150223 | GEO

HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway via stimulating MSK1 kinase and suppressing PPP2R2B protein

Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, which lacks effective therapies. We demonstrated that the transcription factor, HOXC6, was overexpressed in most PDACs, and its inhibition blocked PDAC tumor growth and metastasis. HOXC6 transcriptionally activated the tumor-promoting kinase MSK1. To identify the phosphorylation targets of MSK1 and the mediators of its function in AsPC1 cells, we utilized an unbiased TMT10-based phosphoproteomics analysis. To do so, we treated AsPC1 cells with MSK1 inhibitor SB-747651A and performed TMT10-based quantitative phosphoproteomics analysis and identified MSK1 phosphorylation targets.

2023-10-31 | PXD041239 | Pride

HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway via stimulating MSK1 kinase and suppressing PPP2R2B protein

Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, which lacks effective therapies. We demonstrated that the transcription factor, HOXC6, was overexpressed in most PDACs, and its inhibition blocked PDAC tumor growth and metastasis. HOXC6 transcriptionally activated the tumor-promoting kinase MSK1. To identify the phosphorylation targets of MSK1 and the mediators of its function in PANC1 cells, we utilized an unbiased TMT10-based phosphoproteomics analysis. To do so, we treated AsPC1 cells with MSK1 inhibitor SB-747651A and performed TMT10-based quantitative phosphoproteomics analysis and identified MSK1 phosphorylation targets.

2023-10-31 | PXD041238 | Pride

HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway via stimulating MSK1 kinase and suppressing PPP2R2B protein

Project description:HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway via stimulating MSK1 kinase and suppressing PPP2R2B protein

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HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway via stimulating MSK1 kinase and suppressing PPP2R2B protein

Project description:HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway via stimulating MSK1 kinase and suppressing PPP2R2B protein

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A therapeutically targetable NOTCH1-SIRT1-KAT7 axis in T-ALL

Project description:A therapeutically targetable NOTCH1-SIRT1-KAT7 axis in T-ALL

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siRNA profiling of human LNCaP cells overexpressing/knockdown of HOXC6

Project description:The transcription factor HOXC6 is upregulated in human prostate cancer. SiRNA knockdown of HOXC6 induces apoptosis in LNCaP cells while upregulation rescued LNCaP cells from siRNA-induced apoptosis. We used microarrays to identify the genes whose expression underly the anti-apoptotic and proliferative effects of HOXC6 in LNCaP cells. Experiment Overall Design: LNCaP cells were transiently transfected with a cocktail of 5 siRNAs to HOXC6 to a final concentration of 100nM, with a HOXC6 gene expression vector, or control siRNA and vector. Cells were collected a 48hours post-transfection

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HOXC6 affects the malignant phenotype of esophageal squamous cell carcinoma cells

Project description:HOXC6 is a member of the HOX family, and its aberrant expression has been verified in a variety of cancers, such as prostate, breast,nasopharyngeal carcinoma,gastric, and ovarian cancers.Some studies suggest that HOXC6 might be involved in tumor initiation and progression.However, the role of HOXC6 in esophageal squamous cell carcinoma cells has not been fully investigated.Here we study how HOXC6 affects the malignant phenotype of esophageal squamous cell carcinoma cells

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