Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TFE3 Xp11.2 translocation renal cell carcinoma mouse model

ABSTRACT: Renal Cell Carcinoma (RCC) associated with Xp11.2 translocation (TFE3-RCC) has been recently defined as a distinct subset of RCC. The Xp11 translocations involve the TFE3 transcription factor and produce chimeric TFE3 proteins retaining the basic helix-loop-helix leucine zipper structure for dimerization. To facilitate the development of molecular-based diagnostic tools and targeted therapies for TFE3-RCC, we generated a translocation RCC mouse model and performed DNA microarray analysis.

ORGANISM(S): Mus musculus

PROVIDER: GSE130072 | GEO | 2019/04/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

TFE3-splicing factor fusions represent functional drivers and druggable targets in translocation renal cell carcinoma

Project description:TFE3 is a member of the basic helix-loop-helix leucine zipper MiT transcription factor family and its chimeric proteins are associated with translocation renal cell carcinoma (tRCC). Despite the variety of genes fusions, most of TFE3 fusions partner genes are related to spliceosome machinery. Dissecting the function of TFE3 fused to spliceosome machinery factors (TFE3-SF) could direct the development of effective therapies for this lethal disease, which is refractory to standard treatments for kidney cancer. Here, by using a combination of in silico structure prediction, transcriptome profiling, molecular characterization, and high-throughput high-content screening (HTHCS) we interrogated a number of oncogenic mechanisms of TFE3-SF-containing fusions. We demonstrate that inhibition of TFE3-SF dimerization reverses its oncogenic activity and represents a potential new target for therapeutic intervention. Using HTHCS combined with FRET technology, we screened the FDA approved drugs library LOPAC and a small molecule library (Microsource) and identified compounds that inhibit TFE3-SF dimerization. Hit compounds were validated in 2D and 3D models utilizing patient derived xenolines and xenografts expressing TFE3-SF. The antihistamine terfenadine demonstrated decreased cell proliferation and reduced in vivo tumor growth. Overall, our results unmask synthetic vulnerabilities of TFE3-SF dimerization for novel therapeutic strategies in patients with this aggressive type of kidney cancer.

2023-09-01 | GSE237407 | GEO

TFE3 Xp11.2 translocation renal cell carcinoma mouse model

Project description:TFE3 Xp11.2 translocation renal cell carcinoma mouse model

| PRJNA533790 | ENA

Comparative genomics incorporating translocation renal cell carcinoma mouse model reveals molecular mechanisms of tumorigenesis

Project description:Translocation renal cell carcinoma (tRCC) most commonly involves an ASPSCR1-TFE3 fusion, but molecular mechanisms remain elusive and animal models are lacking. Here, we show that human ASPSCR1-TFE3 driven by Pax8-Cre (a credentialed clear cell RCC driver) disrupted nephrogenesis and glomerular development, causing neonatal death, while the clear cell RCC failed driver, Sglt2-Cre, induced aggressive tRCC (as well as alveolar soft part sarcoma) with complete penetrance and short latency. However, in both contexts, ASPSCR1-TFE3 led to characteristic morphological cellular changes, loss of epithelial markers, and an epithelial-mesenchymal transition. Electron microscopy of tRCC tumors showed lysosome expansion, and functional studies revealed simultaneous activation of autophagy and mTORC1 pathways. Comparative genomic analyses encompassing an institutional human tRCC cohort (including a hitherto unreported SFPQ-TFEB fusion) and a variety of tumorgraft models (ASPSCR1-TFE3, PRCC-TFE3, SFPQ-TFE3, RBM10-TFE3, and MALAT1-TFEB) disclosed significant convergence in canonical pathways (cell cycle, lysosome, and mTORC1) and less established pathways such as Myc, E2F, and inflammation (IL-6/JAK/STAT3, interferon-γ, TLR signaling, systemic lupus, etc.). Therapeutic trials (adjusted for human drug exposures) showed antitumor activity of cabozantinib. Overall, this study provides insight into MiT/TFE-driven tumorigenesis, including the cell of origin, and characterizes diverse mouse models available for research

2024-01-04 | GSE252047 | GEO

Metabolic reprogramming driven by TFE3 fusions unveils novel vulnerabilities in translocation renal cell carcinoma [RNA-Seq]

Project description:Translocation renal cell carcinoma (tRCC) is an aggressive subtype of kidney cancer driven by TFE3 gene fusions, which act via poorly characterized downstream mechanisms. Here we report that TFE3 fusions transcriptionally rewire tRCCs toward oxidative phosphorylation (OXPHOS), contrasting with the highly glycolytic metabolism of most other RCCs. The transcriptional program driven by TFE3 fusions sustains high NRF2 signaling and glutathione production, which offsets reactive oxygen species generated by OXPHOS but renders tRCC cells sensitive to reductive stress. Genome-scale CRISPR screening identifies tRCC-selective vulnerabilities linked to maintaining this metabolic balance, including EGLN1, which hydroxylates HIF-1α and targets it for proteolysis. Inhibition of EGLN1compromises tRCC cell growth by stabilizing HIF-1a and promoting glycolytic reprogramming. Our study defines a distinctive tRCC-essential metabolic program driven by TFE3 fusions and nominates EGLN1inhibition as a therapeutic strategy to counteract fusion-induced metabolic rewiring.

2024-08-10 | GSE266517 | GEO

Tfe3-bound regions in naive pluripotent mouse embryonic stem (ES) cells

Project description:The bHLH transcription factor Tfe3 is a powerful regulator of pluripotency and we report a genome-wide analysis of Tfe3 occupancy in mouse ES cells. Nuclear localization of Tfe3 is inhibited by a protein complex containing the tumor-suppressor Folliculin (Flcn) and we also determine Tfe3 binding sites in ES cells expressing an shRNA targeting Flcn. Specificity is controlled for by using unspecific IgGs and ES cells expressing an shRNA targeting Tfe3. ChIP-Seq profiling of Tfe3 in ES cells

2013-04-10 | E-GEOD-39815 | biostudies-arrayexpress

Hexameric VCP/p97 reprograms transcription by organizing enhancers with the ASPSCR1-TFE3 fusion oncoprotein

Project description:Aberrant transcription in alveolar soft part sarcoma (ASPS) is orchestrated by the fusion oncoprotein, ASPSCR1-TFE3, resulting from a gene fusion created by a t(X;17) chromosomal translocation. Proteomic analysis of co-immunoprecipitated ASPSCR1-TFE3 complexes revealed strong enrichment of VCP/p97, an AAA+ ATPase with known segregase function. VCP and ASPSCR1-TFE3 co-distributed across chromatin and were associated with active enhancers, indicated by flanking peaks of H3K27ac that assemble into higher order chromatin structures by HiChIP. Positive and negative genetic experiments with ASPSCR1-TFE3 and VCP demonstrated that they function co-dependently for cancer cell proliferation, colony formation, enhancer activation, chromatin conformation, and transcription. The VCP associating with ASPSCR1-TFE3 was found by native gel and electron microscopy to be assembled into homo-hexamers. Disruption of VCP hexamer assembly or enzymatic function inhibited the transcriptional impact of ASPSCR1-TFE3. Thus, a segregase was found to bind chromatin and assemble into 3-dimensional structures as a co-factor of transcriptional regulation.

2023-11-23 | PXD022515 | Pride

DETECTION OF FOUR NOVEL RENAL TUMORS CASES HARBORING RBM10-TFE3 FUSIONS

Project description:Microphtalmia-associated-transcriptional-factor-family translocation renal cell carcinoma (MiTF-tRCC) currently includes two main subtypes: “TFEB-tRCC” most often characterized by a t(6;11)(p21;q13) that generates a fusion of TFEB with MALAT1 and “TFE3-tRCC” characterized by rearrangements of TFE3 at Xp11.23 (2-3) that produce a variety of fusion genes. FISH is a handy method in routine practice that allows the detection of a rearrangement of TFE3. However, it reaches its limits in cases of micro-inversions or insertions: in fact paracentric microinversions that involve GRIPAP1 (Xp11.23) (23, Classe) or RBM10 (Xp11.3), very close to TFE3 , are most often undetectable.We report the clinical, immunohistological, genomic and molecular description of four novel TFE3-tRCC with RBM10-TFE3 fusion detected by targeted RNASeq analysis that illustrate the difficulties of diagnosis, especially in reason of disconcerting negative TFE3 FISH results.

2020-11-04 | GSE160731 | GEO

ASPSCR1-TFE3 reprograms transcription by organizing enhancers around hexameric VCP [hASPS_ChIP, ASPL_VCP_Pol2]

Project description:Aberrant transcription in alveolar soft part sarcoma (ASPS) is orchestrated by the fusion oncoprotein, ASPSCR1-TFE3, product of a gene fusion created by a t(X;17) chromosomal translocation. Here, proteomics of proteins co-immunoprecipitating with ASPSCR1-TFE3 revealed strong enrichment of VCP/p97, an AAA+ ATPase with known segregase function. Positive and negative genetic experiments with ASPSCR1-TFE3 and VCP demonstrated that they function co-dependently for cancer cell proliferation, colony formation, enhancer activation, chromatin conformation, and transcription

2023-01-01 | GSE162478 | GEO

ASPSCR1-TFE3 reprograms transcription by organizing enhancers around hexameric VCP [ASPS1 VCP ChIP]

2023-01-01 | GSE162727 | GEO

HA-TFE3 bound regions in HK-2 HA-TFE3-inducible cells

Project description:TFE3 is a bHLH-ZIP transcription factor, which nuclear localization is regulated by a tumor suppressor FLCN. In order to analyze TFE3 occupancy in whole genome, we have generated and utilized a HK-2 HA-TFE3-inducible cell line which express HA-tagged TFE3 in a doxycycline-dependent manner. HA-TFE3 bound regions were determined by ChIPSeq.

2020-08-07 | GSE135490 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data