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The Receptor Tyrosine Kinase AXL is Required at Multiple Steps of the Metastatic Cascade during HER2-positive Breast Cancer Progression

ABSTRACT: The Receptor Tyrosine Kinase AXL is Required at Multiple Steps of the Metastatic Cascade during HER2-positive Breast Cancer Progression

PROVIDER: PRJNA397577 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5909510_1.fastq.gz	Fastqsanger.gz
	SRR5909510_2.fastq.gz	Fastqsanger.gz
	SRR5909511_1.fastq.gz	Fastqsanger.gz
	SRR5909511_2.fastq.gz	Fastqsanger.gz
	SRR5909512_1.fastq.gz	Fastqsanger.gz

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RNA-seq of MMTV-Neu AXL KO tumors

Project description:AXL is activated by its ligand GAS6 and is expressed in triple-negative breast cancer cells. We report that AXL is also detected in HER2+ breast cancer specimens where its expression correlates with poor patients’ survival. Using murine models of HER2+ breast cancer, AXL, but not Gas6, was found essential for metastasis. We determined that AXL is required for intravasation, extravasation and growth at the metastatic site. AXL is expressed in HER2+ cancers displaying EMT signatures and contributes to sustain EMT in murine tumors. Interfering with AXL in patient-derived xenograft impaired TGF-β-induced cell invasion. Lastly, pharmacological inhibition of AXL decreased the metastatic burden of mice developing HER2+ breast cancer. Our data identify AXL as a potential co-therapeutic target during the treatment of HER2+ breast cancers to limit metastasis.

2018-05-01 | GSE102368 | GEO

Identification of the receptor tyrosine kinase AXL in triple negative breast cancer as a novel target for the human miR-34a microRNA

Project description:This SuperSeries is composed of the following subset Series: GSE21719: Identification of the receptor tyrosine kinase AXL in triple negative breast cancer as a novel target for the human miR-34a microRNA (miRNA study) GSE21832: Identification of the receptor tyrosine kinase AXL in triple negative breast cancer as a novel target for the human miR-34a microRNA (gene expression) Refer to individual Series

2010-12-31 | E-GEOD-21834 | biostudies-arrayexpress

RNA-seq of MMTV-Neu AXL KO tumor grafts in FVB

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Quantitative tyrosine phosphoproteome profiling of GAS6-AXL signaling network

Project description:Overexpression and amplification of AXL receptor tyrosine kinase (RTK) has been found in several hematologic and solid malignancies. Activation of AXL by its ligand GAS6 can enhance tumor-promoting processes such as proliferation, migration, invasion, and survival. Despite the important role of AXL in cancer development, a deep and quantitative mapping of its signaling transduction has not been performed. Here, we used a mass spectrometry-based quantitative proteomic approach to characterize the temporal dynamics of the phosphotyrosine proteome of MDA-MB-231 cells stimulated with GAS6

2021-08-24 | PXD025457 | Pride

The Receptor Tyrosine Kinase AXL is Required at Multiple Steps of the Metastatic Cascade during HER2-positive Breast Cancer Progression

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

2018-05-01 | GSE102370 | GEO

Effect of Gas6/Axl on HCC cell line gene expression

Project description:We adressed the impact of the receptor tyrosine kinase Axl and ist ligand Gas6 on gene expression in cellular HCC models, including cells harbouring Axl KO and exogenous reexpression.

2023-04-20 | GSE229731 | GEO

Axl targeting in experimental unilateral ureteral obstruction

Project description:We investigated if Axl receptor tyrosine kinase was up-regulated in unilateral ureteral obstruction (UUO) and if blocking of Axl by a small molecule called BGB324 (also called Bemcentinib) reduces fibrosis development in the ligated kidney as compared to treatment with its vehicle alone.

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Inhibition of AXL Receptor Tyrosine Kinase Enhances Brown Adipose Tissue Functionality in mice [NovaSeq]

Project description:To identify transcriptomic differences in interscapular brown adipose tissue depots from HFD-challenged wild-type (Axl-floxed Cre-) vs. iFAXLKO (Axl-floxed Cre+) mice

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Inhibition of AXL Receptor Tyrosine Kinase Enhances Brown Adipose Tissue Functionality in mice [HiSeq]

Project description:To identify transcriptomic differences in interscapular brown adipose tissue depots from HFD-challenged wild-type (WT) vs. Axl KO (whole-body Axl Receptor knockout) mice

2023-06-22 | GSE231469 | GEO

The effect of inhibition of receptor tyrosine kinase AXL on DNA damage response in ovarian cancer

Project description:AXL is a receptor tyrosine kinase that is often overexpressed in cancers. It contributes to pathophysiology in cancer progression and therapeutic resistance, making it an emerging therapeutic target. The first-in-class AXL inhibitor bemcentinib (R428/BGB324) has been granted fast track designation by the U.S. Food and Drug Administration (FDA) in STK11-mutated advanced metastatic non-small cell lung cancer and was also reported to show selective sensitivity towards ovarian cancers (OC) with a Mesenchymal molecular subtype. In this study, we further explored AXL’s role in mediating DNA damage responses by using OC as a disease model. AXL inhibition using R428 resulted in the increase of DNA damage with the concurrent upregulation of DNA damage response signalling molecules. Furthermore, AXL inhibition rendered cells more sensitive to the inhibition of ATR, a crucial mediator for replication stress. Combinatory use of AXL and ATR inhibitors showed additive effects in OC. Through SILAC co-immunoprecipitation mass spectrometry, we identified a novel binding partner of AXL, SAM68, whose loss in OC cells harboured phenotypes in DNA damage responses similar to AXL inhibition. In addition, AXL- and SAM68-deficiency or R428 treatment induced elevated levels of cholesterol and upregulated genes in the cholesterol biosynthesis pathway. There might be a novel protective role of cholesterol in shielding cancer cells against DNA damage induced by AXL inhibition or SMA68 deficiency.

2023-06-22 | PXD042572 | Pride

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