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RNA-seq of pancreatic CAF-derived cell line 0082T treated with Autotaxin inhibitors (IOA-289 and PF-8380) against DMSO treated controls

ABSTRACT: RNA-seq of pancreatic CAF-derived cell line 0082T treated with Autotaxin inhibitors (IOA-289 and PF-8380) against DMSO treated controls

PROVIDER: PRJEB80799 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR13757700_1.fastq.gz	Fastqsanger.gz
	ERR13757700_2.fastq.gz	Fastqsanger.gz
	ERR13757701_1.fastq.gz	Fastqsanger.gz
	ERR13757701_2.fastq.gz	Fastqsanger.gz
	ERR13757702_1.fastq.gz	Fastqsanger.gz

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RNA-seq of pancreatic CAF-derived cell line 0082T treated with Autotaxin inhibitors (IOA-289 and PF-8380) against DMSO treated controls

Project description:Autotaxin (ATX), encoded by ENPP2, catalyzes the production of lysophosphatidic acid (LPA), an important regulator within the tumor microenvironment (TME). ATX is a clinical target in pancreatic ductal adenocarcinoma (PDAC), yet the pro-tumorigenic action of the ATX/LPA axis in PDAC remains unclear. PDAC is characterized by a highly fibrotic tumor microenvironment (TME) due to an abundance of cancer associated fibroblasts (CAFs), acting as a barrier to therapy and contributing to the poor survival of PDAC patients. The mechanism by which ATX inhibition influences CAFs and their secretome is still not fully characterized. To identified potential downstream mediators of ATX signaling, we performed RNA-seq of pancreatic CAF-derived cell line 0082T treated with Autotaxin inhibitors, IOA-289 and PF-8380. PF-8380 treatment resulted in a higher number of differentially expressed genes compared to IOA-289 treatment. IOA-289 treatment resulted in only four significantly differentially expressed genes (CTGF, PLIN2, HHIP, and AHNAK). However, only PLIN2, which was upregulated and CTGF, which was downregulated, overlapped between the two ATX inhibitors. As CTGF (connective tissue growth factor) is a pro-fibrotic and pro-tumorigenic factor, it suggests a key role for CAF-derived ATX in promoting autocrine and paracrine pro-tumorigenic signaling in PDAC.

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