Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pancreatic cancer-intrinsic HuR regulates the pro-tumorigenic properties of extracellular vesicles

ABSTRACT: Pancreatic cancer-intrinsic HuR regulates the pro-tumorigenic properties of extracellular vesicles

PROVIDER: PRJNA1294213 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Pancreatic cancer-intrinsic HuR regulates the pro-tumorigenic properties of extracellular vesicles

Project description:Pancreatic ductal adenocarcinoma (PDAC) tumors contain chaotic vasculature that limits immune surveillance and promotes early events in the metastatic cascade. However, current antiangiogenic therapies have failed in PDAC, and it remains important to uncover mechanisms by which cancer cells signal to endothelial cells to increase angiogenesis. The tumor-intrinsic RNA-binding protein HuR (ELAVL1) plays an important role re-shaping the tumor microenvironment (TME) by regulating the stability and translation of cytokine encoding transcripts. PDAC-intrinsic HuR influenced endothelial cell function in the TME via extracellular vesicle (EV) signaling, an underexplored signaling axis in tumor progression. HuR knockout (KO) tumors had impaired growth in an immunocompetent mouse model, and that administering purified wildtype (WT) EVs increased tumor growth. Further, isobaric-labeling quantitative proteomics showed that PDAC EVs contained HuR-dependent cargos relating to endothelial cell function and angiogenesis. Treatment of endothelial cells with HuR WT EVs strongly increased the expression of genes involved in barrier function, endothelial cell development, and directly increased their migratory and tube forming functions. In an immunocompetent orthotopic mouse model of PDAC, HuR increased endothelial cell presence and sprouting, while decreasing ICAM-1 expression. When utilizing the PalmGRET genetic EV reporter, decreased ICAM-1 within WT tumors occurred in endothelial cells that had imported PDAC EVs, suggesting signaling that directly modulates endothelial cell behavior in vivo. Collectively, our data reveal a new role of HuR in EV signaling to endothelial cells, promoting angiogenesis while restricting endothelial cell leukocyte trafficking behavior.

2025-08-09 | PXD059674 | Pride

Pancreatic cancer-intrinsic HuR regulates the pro-tumorigenic properties of extracellular vesicles

Project description:Pancreatic ductal adenocarcinoma (PDAC) tumors contain chaotic vasculature that limits immune surveillance and promotes early events in the metastatic cascade. However, current antiangiogenic therapies have failed in PDAC, and thus, it remains important to uncover mechanisms by which cancer cells signal to endothelial cells to increase angiogenesis. Our lab has shown that the tumor-intrinsic RNA-binding protein HuR (ELAVL1) plays an important role re-shaping the tumor microenvironment (TME) by regulating the stability and translation of cytokine encoding transcripts. Herein, we demonstrate that PDAC-intrinsic HuR influences endothelial cell function in the TME via extracellular vesicle (EV) signaling, an underexplored signaling axis in tumor progression. We found that HuR knockout (KO) tumors have impaired growth in an immunocompetent mouse model, and that administering purified wildtype (WT) EVs can increase tumor growth. Further, we observed that PDAC EVs contain HuR-dependent cargoes relating to endothelial cell function and angiogenesis. Treatment of endothelial cells with HuR WT EVs strongly increased the expression of genes involved in barrier function and endothelial cell development, and directly increased their migratory and tube forming functions. In an immunocompetent orthotopic mouse model of PDAC, we showed that HuR increases endothelial cell presence and sprouting, while decreasing ICAM-1 expression. Importantly, we found utilizing a genetic EV reporter, that decreased ICAM-1 within WT tumors occurs in endothelial cells that have imported PDAC EVs, suggesting that this signaling axis is directly modulating endothelial cell behavior in vivo. Collectively, our data reveal a new role of HuR in EV signaling to endothelial cells, promoting angiogenesis while restricting endothelial cell leukocyte trafficking behavior.

2025-08-09 | GSE303131 | GEO

Tumorigenic iPSC-NS/PCs with mesenchymal properties

Project description:Tumorigenic iPSC-NS/PCs with mesenchymal properties

| PRJNA699371 | ENA

Hypoxia controls the glycobiological signature and related pro-tumorigenic properties of metastatic melanomas

Project description:Hypoxia controls the glycobiological signature and related pro-tumorigenic properties of metastatic melanomas

| PRJNA780950 | ENA

Cell-intrinsic tumorigenic functions of PPARg in bladder urothelial carcinoma

Project description:Cell-intrinsic tumorigenic functions of PPARg in bladder urothelial carcinoma

| PRJNA701983 | ENA

Cell-intrinsic tumorigenic functions of PPARg in bladder urothelial carcinoma [ChIP-seq]

Project description:Cell-intrinsic tumorigenic functions of PPARg in bladder urothelial carcinoma [ChIP-seq]

| PRJNA702004 | ENA

Cell-intrinsic tumorigenic functions of PPARg in bladder urothelial carcinoma [RNA-seq]

Project description:Cell-intrinsic tumorigenic functions of PPARg in bladder urothelial carcinoma [RNA-seq]

| PRJNA702003 | ENA

Hypoxia controls the glycobiological signature and related pro-tumorigenic properties of metastatic melanomas

Project description:Metastatic melanoma (MM) has a five-year survival rate of only 37%. The major causes of MM-related mortality are distant organ involvement and treatment resistance. These metastatic activities are often potentiated by the persistence of tumor-initiating cells (TICs) thriving in areas of hypoxia. To enhance therapy success, it is, thus, critical to understand MM TIC properties and devise MM TIC-specific treatment strategies. Our recent data suggest that MM cells have a distinct MM glycome signature characterized by fetal i-linear poly-N-acetyllactosamines (poly-LacNAc) and loss of I-branching enzyme β1,6 N-acetylglucosaminyltransferase 2 (GCNT2) that promote tumorigenicity. Whether hypoxia can instruct MM TIC development by modulating the MM glycome signature remains unknown. Here, comparative analysis of GCNT2 levels on patient melanoma cells and clinical outcome confirmed the relationship between loss of GCNT2 and poor patient survival. Moreover, MM cells with low GCNT2 showed elevated TIC marker expression and increased TIC potential, in vivo. Under hypoxia, MM cells further lost GCNT2 and I-branched poly-LacNAc expression and showed corresponding elevations in TIC markers and other glycome-related alterations. Galectin (Gal)-8, notably, was upregulated under hypoxia, preferred binding to i-linear poly-LacNAcs, increased TIC marker CD271, and was significantly elevated in sera of melanoma patients. Knockdown of Gal-8 in MM cells significantly decreased CD271 levels, even under hypoxia. Results from this investigation reveal a key role for hypoxia in enforcing the MM glycome signature and for Gal-8 as a pro-tumorigenic lectin and putative biomarker of MM.

2022-08-03 | GSE188986 | GEO

Intrinsic mesoscale properties of a Polycomb protein underpin heterochromatin fidelity

Project description:Intrinsic mesoscale properties of a Polycomb protein underpin heterochromatin fidelity

| PRJNA802231 | ENA

Cytoplasmic overexpression of RNA-binding protein HuR in meningioma is a marker of poor prognosis and specific HuR knockdown decreases meningioma cell growth and resistance to hypoxia

Project description:HuR is known to regulate mRNA stability and translatability in cytoplasm. In several human tumors, the level of HuR expression has been shown to correlate with poor disease outcome. In meningioma, however, the prognostic value and the potential pro-oncogenic properties of HuR remain obscure. To clarify these, transcriptome-wide analyses in IOMM-Lee cells were performed to pinpoint the detailed molecular consequences of HuR knockdown. In IOMM-Lee cells, transcriptomic analyses revealed that HuR knockdown deregulated the signaling pathway of HIF1A and upregulated the expression of genes for cytoplasmic mRNA processing body assembly, poly(A)-specific ribonuclease activity, positive regulation of apoptosis, negative regulation of RNA splicing, global genome nucleotide-excision repair, and positive regulation of cell cycle arrest. Interestingly, HuR knockdown under hypoxic culture condition potentiated further the effects of HuR knockdown on cell growth, apoptosis, and HIF1A expression.

2017-05-11 | GSE95212 | 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