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Reelin-LRP8 signaling mediates brain metastasis of breast cancer cells via abluminal migration

ABSTRACT: Reelin-LRP8 signaling mediates brain metastasis of breast cancer cells via abluminal migration

PROVIDER: PRJNA1221936 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32300992_1.fastq.gz	Fastqsanger.gz
	SRR32300992_2.fastq.gz	Fastqsanger.gz
	SRR32300993_1.fastq.gz	Fastqsanger.gz
	SRR32300993_2.fastq.gz	Fastqsanger.gz
	SRR32300994_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Reelin-LRP8 signaling mediates brain metastasis of breast cancer cells via abluminal migration

Project description:Brain metastasis (BM) remains a significant challenge in breast cancer (BC) management. While conventional metastatic routes involve hematogenous dissemination, emerging evidence suggests that BC cells can also migrate along the abluminal surface of blood vessels, bypassing the blood-brain barrier (BBB). To investigate this phenomenon, we established a zebrafish xenograft model utilizing GFP-labeled MDA-MB-231 cells, allowing real-time observation of BC cell migration along the posterior cerebral veins. Our findings revealed that LRP8, a apolipoprotein E receptor, is upregulated in BC patients with brain metastases. Functional studies demonstrated that LRP8 knockdown significantly inhibited proliferation, migration, and invasion of triple-negative breast cancer (TNBC) cells both in vitro and in vivo. Mechanistically, LRP8 promotes the activation of CDC42, enhancing filopodia formation and cell motility, a process influenced by the neuronal extracellular matrix protein, Reelin. Furthermore, we demonstrate the therapeutic potential of MEN 10207, a neurokinin-2 receptor antagonist, in inhibiting TNBC cell migration and suppressing BM formation in both zebrafish and mouse models. These findings provide novel insights into the mechanisms underlying extravascular brain metastasis in BC, highlighting the Reelin-LRP8-CDC42 axis as a potential therapeutic target for this devastating complication.

2025-05-22 | GSE289226 | GEO

LRP8-Reelin-regulated Neuronal (LRN) Enhancer signature underlying learning and memory formation (RNA-Seq 1)

Project description:A comprehensive landscape of epigenomic events regulated by the Reelin signaling through activation of specific cohort of cis-regulatory enhancer elements (LRN-enhancers), which involves the proteolytical processing of the LRP8 receptor by the gamma-secretase activity and is required for learning and memory behavior All RNA-Seq experiments were designed to evaluate the transcriptional program regulated by the Reelin-LRP8 signaling pathway in neuronal cells

2015-04-29 | E-GEOD-66706 | biostudies-arrayexpress

LRP8-Reelin-regulated Neuronal (LRN) Enhancer signature underlying learning and memory formation (RNA-Seq 2)

2015-04-29 | E-GEOD-66707 | biostudies-arrayexpress

LRP8-Reelin-regulated Neuronal (LRN) Enhancer signature underlying learning and memory formation (GRO-seq)

Project description:A comprehensive landscape of epigenomic events regulated by the Reelin signaling through activation of specific cohort of cis-regulatory enhancer elements (LRN-enhancers), which involves the proteolytical processing of the LRP8 receptor by the gamma-secretase activity and is required for learning and memory behavior All GRO-Seq experiments were designed to understand the unique signature of LRN-enhancers and to evaluate the transcriptional response to Reelin treatment in neuronal cells.

2015-04-29 | E-GEOD-66703 | biostudies-arrayexpress

LRP8-Reelin-regulated Neuronal (LRN) Enhancer signature underlying learning and memory formation (GRO-seq)

2015-04-29 | GSE66703 | GEO

LRP8-Reelin-regulated Neuronal (LRN) Enhancer signature underlying learning and memory formation (ChIP-Seq)

2015-04-29 | GSE66701 | GEO

LRP8-Reelin-regulated Neuronal (LRN) Enhancer signature underlying learning and memory formation (4C-Seq)

2015-04-29 | GSE66709 | GEO

LRP8-Reelin-regulated Neuronal (LRN) Enhancer signature underlying learning and memory formation (RNA-Seq 2)

2015-04-29 | GSE66707 | GEO

LRP8-Reelin-regulated Neuronal (LRN) Enhancer signature underlying learning and memory formation (RNA-Seq 1)

2015-04-29 | GSE66706 | GEO

RAS signalling through PI3-Kinase controls cell migration via modulation of Reelin expression

Project description:RAS signalling through Phosphoinositide 3-kinase (PI3-Kinase) has been shown to have an essential role in tumour initiation and maintenance. RAS also regulates cell motility and tumor invasiveness, but the role of direct RAS binding to PI3-Kinase in this remains uncertain. Here, we provide evidence that disruption of RAS interaction with PI3-Kinase p110adecreases cell motility and prevents activation of Rac GTPase. Analysis of gene expression in cells lacking RAS interaction with p110areveals increased levels of the extracellular matrix glycoprotein Reelin and activation of its downstream pathway resulting in upregulation of E-Cadherin expression. Induction of the Reelin / E-Cadherin axis is also observed in Kras mutant lung tumours that are regressing due to blockade of RAS interaction with PI3-Kinase. Furthermore, loss of Reelin correlates with decreased survival of lung and breast cancer patients. Reelin thus plays a role in restraining RAS and PI3-kinase promotion of cell motility and potentially tumour metastasis.

2016-02-12 | GSE77843 | GEO

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