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HDAC2 facilitates metastasis of pancreatic cancer cells

ABSTRACT: HDAC2 facilitates pancreatic cancer metastasis

PROVIDER: PRJEB47385 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR7222220.fastq.gz	Fastqsanger.gz
	ERR7222230.fastq.gz	Fastqsanger.gz
	ERR7222221.fastq.gz	Fastqsanger.gz
	ERR7222231.fastq.gz	Fastqsanger.gz
	ERR7222212.fastq.gz	Fastqsanger.gz

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HDAC2 Facilitates Pancreatic Cancer Metastasis.

Project description:The mortality of patients with pancreatic ductal adenocarcinoma (PDAC) is strongly associated with metastasis, a multistep process that is incompletely understood in this disease. Although genetic drivers of PDAC metastasis have not been defined, transcriptional and epigenetic rewiring can contribute to the metastatic process. The epigenetic eraser histone deacetylase 2 (HDAC2) has been connected to less differentiated PDAC, but the function of HDAC2 in PDAC has not been comprehensively evaluated. Using genetically defined models, we show that HDAC2 is a cellular fitness factor that controls cell cycle in vitro and metastasis in vivo, particularly in undifferentiated, mesenchymal PDAC cells. Unbiased expression profiling detected a core set of HDAC2-regulated genes. HDAC2 controlled expression of several prosurvival receptor tyrosine kinases connected to mesenchymal PDAC, including PDGFRα, PDGFRβ, and EGFR. The HDAC2-maintained program disabled the tumor-suppressive arm of the TGFβ pathway, explaining impaired metastasis formation of HDAC2-deficient PDAC. These data identify HDAC2 as a tractable player in the PDAC metastatic cascade. The complexity of the function of epigenetic regulators like HDAC2 implicates that an increased understanding of these proteins is needed for implementation of effective epigenetic therapies.SignificanceHDAC2 has a context-specific role in undifferentiated PDAC and the capacity to disseminate systemically, implicating HDAC2 as targetable protein to prevent metastasis.

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Role of Hdac2 in pancreatic ductal adenocarcinoma

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HDAC2 maintains receptor tyrosine kinase signaling of undifferentiated pancreatic cancer cells (ChIP-Seq)

Project description:H3K27ac ChIP-se and ATAC-seq were used to determine epigenetic differences between Hdac2 knockout versus Hdac2 wildtype pancreatic cancer cells.

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Engrailed-1 Promotes Pancreatic Cancer Metastasis

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STN1 facilitates metastasis by promoting transcription of EMT-activator ZEB1 in pancreatic cancer

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S100P is a metastasis-associated gene that facilitates transendothelial migration of pancreatic cancer cells [HG-U133B]

Project description:Pancreatic cancer is a devastating disease with both local invasion and distant metastasis. Identifying the genes expressed in liver metastases and signatures of metastatic progression would therefore be of particular importance as they could aid in both recurrence prediction as well as representing novel therapeutic targets. Keywords: Gene expression profiling We have performed microarray gene expression analysis of normal pancreas, primary pancreatic ductal adenocarcinoma (PDAC), normal liver and pancreatic liver metastases to identify potential therapeutic targets.

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2023-09-12 | GSE242662 | GEO

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