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ASCL1 is activated downsrteam of ROR2/CREB signaling pathway to support lineage plasticity [ChIP-seq]

ABSTRACT: ASCL1 is activated downsrteam of ROR2/CREB signaling pathway to support lineage plasticity [ChIP-seq]

PROVIDER: PRJNA930907 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23325121.fastq.gz	Fastqsanger.gz
	SRR23325122.fastq.gz	Fastqsanger.gz
	SRR23325123.fastq.gz	Fastqsanger.gz
	SRR23325124.fastq.gz	Fastqsanger.gz
	SRR23325125.fastq.gz	Fastqsanger.gz

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ASCL1 is activated downsrteam of ROR2/CREB signaling pathway to support lineage plasticity [ChIP-seq]

Project description:Lineage plasticity has been shown to be a form of therapy-induced drug resistance. In prostate cancer, androgen receptor (AR) pathway inhibitors have led to accretion of tumor relapse with loss of AR signaling and a shift from a luminal state to an alternate program. Although different genomic and epigenomic aberrations have been correlated with lineage reprogramming, the molecular and signaling mechanisms orchestrating the development of lineage plasticity under the pressure of AR-targeted therapies are not fully understood. Here, a survey of receptor tyrosine kinases (RTKs) identified ROR2 as the top-upregulated RTK following AR pathway inhibition, which feeds into lineage plasticity by promoting stem cell-like and neuronal networks. Mechanistically, we demonstrated that ROR2 activates the ERK/CREB signaling pathway to modulate the expression of the lineage commitment transcription factor, ASCL1. Collectively, our findings nominate ROR2 as a potential therapeutic target to reverse the ENZ-induced plastic phenotype and potentially re-sensitize tumors to AR pathway inhibitors.

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ASCL1 is activated downsrteam of ROR2/CREB signaling pathway to support lineage plasticity [RNA-seq]

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ASCL1 is activated downsrteam of ROR2/CREB signaling pathway to support lineage plasticity.

Project description:ASCL1 is activated downsrteam of ROR2/CREB signaling pathway to support lineage plasticity.

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ASCL1 is activated downsrteam of ROR2/CREB signaling pathway to support lineage plasticity [RNA-seq]

Project description:ASCL1 is activated downsrteam of ROR2/CREB signaling pathway to support lineage plasticity [RNA-seq]

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ASCL1 is activated downsrteam of ROR2/CREB signaling pathway to support lineage plasticity.

Project description:This SuperSeries is composed of the SubSeries listed below.

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Project description:Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells to precancerous lesions to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We found that normal acinar cell differentiation, maintained by the transcription factor Pdx1, suppresses a broad gastric cell identity that is maintained in metaplasia, neoplasia, and the classical subtype of PDAC in mouse and human. We have identified the receptor tyrosine kinase Ror2 as marker of a gastric metaplasia (SPEM)-like identity in the pancreas. Ablation of Ror2 in a mouse model of pancreatic tumorigenesis promoted a switch to a gastric pit cell identity that largely persisted through progression to carcinoma. In both human and mouse pancreatic cancer, ROR2 activity continued to antagonize the gastric pit cell identity, strongly promoting an epithelial to mesenchymal transition, conferring resistance to KRAS inhibition, and vulnerability to AKT inhibition.

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