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YAP1-TFE3 mediates endothelial to mesenchymal transition in epithelioid hemangioendothelioma

ABSTRACT: YAP1-TFE3 mediates endothelial to mesenchymal transition in epithelioid hemangioendothelioma

PROVIDER: PRJNA1214710 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR32091176_1.fastq.gz	Fastqsanger.gz
	SRR32091176_2.fastq.gz	Fastqsanger.gz
	SRR32091177_1.fastq.gz	Fastqsanger.gz
	SRR32091177_2.fastq.gz	Fastqsanger.gz

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YAP1-TFE3 mediates endothelial to mesenchymal transition in epithelioid hemangioendothelioma

Project description:Epithelioid Hemangioendothelioma (EHE) is an ultra-rare vascular sarcoma with a high metastatic rate and a lack of reliable prognostic markers. Because of its rarity, EHE is an understudied disease with limited research tools and few effective treatment options. A thorough understanding of the molecular underpinnings that drive EHE tumorigenesis and facilitate metastasis is essential to discovery of druggable targets that could improve patient outcomes. To better understand this EHE biology we generated transgenic endothelial EHE cell models and observed robust transformation of YAP1-TFE3 (YT) expressing cells resulting in a pro-migratory, anti-apoptotic phenotype. We identified endothelial to mesenchymal transition (EndMT) as a contributing process to this transformation as evidenced by the loss of enothelial gene expression and strong increases in EndMT biomarkers Acta2 and Tgm2. To understand the underlying drivers of this process, we utilized mutant versions of YT and pharmacologic inhibitors to determine that the DNA-binding and dimerization bHLH-LZ domain of YT was necessary for EndMT to occur while canonical TEAD activation was dispensable. This project sheds light on molecular mechanisms of EHE which directly contribute to endothelial transformation.

2025-05-31 | GSE287795 | GEO

RNA-Seq of Human Epithelioid Hemangioendothelioma

Project description:RNA-Seq of Human Epithelioid Hemangioendothelioma

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RNA-Seq of Epithelioid Hemangioendothelioma cell lines

Project description:Epithelioid hemangioendothelioma (EHE) is a rare vascular sarcoma that is associated with a WWTR1-CAMTA1 fusion gene in greater than 90% of cases. Cell lines were generated from WWTR1-CAMTA1 positive murine EHE tumors which also harbor a loss of CDKN2A. RNA sequencing was performed on cell lines.

2022-12-16 | GSE220539 | GEO

RNA-Seq of Human Epithelioid Hemangioendothelioma

Project description:Epithelioid hemangioendothelioma (EHE) is a rare vascular sarcoma that is associated with a WWTR1-CAMTA1 fusion gene in greater than 90% of cases. We aimed to investigate the transcriptional pathways activated in EHE. Total RNA was isolated from EHE tumors from surgical resection or autopsy specimens (n=6) followed by RNA-Seq. The results of this study identified a unique transcriptional profile for EHE and helped to validate a novel murine model of EHE.

2021-03-25 | GSE168493 | GEO

RNA-Seq of Epithelioid Hemangioendothelioma cell lines

Project description:RNA-Seq of Epithelioid Hemangioendothelioma cell lines

| PRJNA910164 | ENA

Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma.

Project description:Conventional epithelioid hemangioendotheliomas (EHE) have a distinctive morphologic appearance and are characterized by a recurrent t(1;3) translocation, resulting in a WWTR1-CAMTA1 fusion gene. We have recently encountered a fusion-negative subset characterized by a somewhat different morphology, including focally well-formed vasoformative features, which was further investigated for recurrent genetic abnormalities. Based on a case showing strong transcription factor E3 (TFE3) immunoreactivity, fluorescence in situ hybridization (FISH) analysis for TFE3 gene rearrangement was applied to the index case as well as to nine additional cases, selected through negative WWTR1-CAMTA1 screening. A control group, including 18 epithelioid hemangiomas, nine pseudomyogenic HE, and three epithelioid angiosarcomas, was also tested. TFE3 gene rearrangement was identified in 10 patients, with equal gender distribution and a mean age of 30 years old. The lesions were located in somatic soft tissue in six cases, lung in three and one in bone. One case with available frozen tissue was tested by RNA sequencing and FusionSeq data analysis to detect novel fusions. A YAP1-TFE3 fusion was thus detected, which was further validated by FISH and reverse transcription polymerase chain reaction (RT-PCR). YAP1 gene rearrangements were then confirmed in seven of the remaining nine TFE3-rearranged EHEs by FISH. No TFE3 structural abnormalities were detected in any of the controls. The TFE3-rearranged EHEs showed similar morphologic features with at least focally, well-formed vascular channels, in addition to a variably solid architecture. All tumors expressed endothelial markers, as well as strong nuclear TFE3. In summary, we are reporting a novel subset of EHE occurring in young adults, showing a distinct phenotype and YAP1-TFE3 fusions.

| S-EPMC4089994 | biostudies-literature

The TAZ-CAMTA1 and YAP-TFE3 fusion proteins modulate the basal TAZ/YAP transcriptional program by recruiting the Ada2a-containing histone acetyltransferase complex [rnaseq_3T3]

Project description:The WWTR1(TAZ)-CAMTA1 and YAP1-TFE3 gene fusions are disease defining gene alterations for epithelioid hemangioendothelioma, a vascular cancer. The resultant fusion proteins fuse the C terminus of CAMTA1 and TFE3 in frame to the N terminus of TAZ and YAP, respectively. An unbiased BioID-mass spectrometry/RNAi screen identified YEATS2 and ZZZ3 as components of the Ada2a-containing histone acetyltransferase complex and key interactors of both TAZ-CAMTA1 and YAP-TFE3. An integrative NGS approach including RNA-Seq, ChIP-Seq, and ATAC-Seq showed TAZ-CAMTA1 and YAP-TFE3 transcriptional programs overlap with TAZ and YAP but also drive expression of a novel transcriptome.

2020-12-01 | GSE152736 | GEO

scRNA-Seq of Cdkn2a mutant murine Epithelioid Hemangioendothelioma tumors

Project description:Epithelioid hemangioendothelioma (EHE) is a rare vascular sarcoma that is associated with a TAZ-CAMTA1 fusion in greater than 90% of cases and loss of CDKN2A in human EHE tumors is associated with late stage disease. Murine EHE tumors were created by conditionally expressing TAZ-CAMTA1 and conditionally knocking out Cdkn2a within vascular endothelium. Resultant tumors were used for single cell RNA sequencing and compared against age matched wild type mice tissue.

2022-12-16 | GSE220540 | GEO

The TAZ-CAMTA1 and YAP-TFE3 fusion proteins modulate the basal TAZ/YAP transcriptional program by recruiting the Ada2a-containing histone acetyltransferase complex [RNA-seq]

Project description:The WWTR1(TAZ)-CAMTA1 and YAP1-TFE3 gene fusions are disease defining gene alterations for epithelioid hemangioendothelioma, a vascular cancer. The resultant fusion proteins fuse the C terminus of CAMTA1 and TFE3 in frame to the N terminus of TAZ and YAP, respectively. An unbiased BioID-mass spectrometry/RNAi screen identified YEATS2 and ZZZ3 as components of the Ada2a-containing histone acetyltransferase complex and key interactors of both TAZ-CAMTA1 and YAP-TFE3. An integrative NGS approach including RNA-Seq and ATAC-Seq showed that the differentially expressed genes in YAP-TFE3 cells with knockdown of YEATS2 or ZZZ3 are nested in regions of open chromatin unique to YAP-TFE3. The altered transcriptional program of the fusion proteins is modulated by the Ada2a-containing histone acetyltransferase complex.

2021-03-04 | GSE168205 | GEO

The TAZ-CAMTA1 and YAP-TFE3 fusion proteins modulate the basal TAZ/YAP transcriptional program by recruiting the Ada2a-containing histone acetyltransferase complex [atacseq]

2020-12-01 | GSE152733 | GEO