Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

EWI-2 regulates melanoma growth and lung metastasis in a TGF-M-NM-21-dependent manner

ABSTRACT: EWI-2 (IgSF8) plays a novel, bifunctional role in melanoma cells. EWI-2 inhibits migration, metastasis, EMT-like changes, and CD271-dependent invasion in multiple melanoma cell lines. On the other hand, EWI-2 supports melanoma cell proliferation, survival, and xenograft growth. Consistent with these results, EWI-2 levels were elevated in human malignant melanoma, but not in metastatic melanoma samples. Altered melanoma cell functions, caused by EWI-2 ablation, are almost entirely dependent on enhanced TRF-M-NM-21 signaling, and also require contributions from tetraspanin proteins CD9 and CD81. In melanoma cells lacking EWI-2, tetraspanins CD9 and CD81 enhance TRF-M-NM-21 signaling by facilitating TM-NM-2R-2M-bM-^HM-^RTM-NM-2R-1 receptor complex formation. When EWI-2 is present, CD9 and CD81 are diverted into EWI-2 complexes, and thus TRF-M-NM-21 signaling is inhibited. 4 samples = 2 Control + 2 EWI-2 KD.

ORGANISM(S): Homo sapiens

SUBMITTER: Konstantin Knoblich

PROVIDER: E-GEOD-47978 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

EWI-2 regulates melanoma growth and lung metastasis in a TGF-β1-dependent manner

Project description:EWI-2 (IgSF8) plays a novel, bifunctional role in melanoma cells. EWI-2 inhibits migration, metastasis, EMT-like changes, and CD271-dependent invasion in multiple melanoma cell lines. On the other hand, EWI-2 supports melanoma cell proliferation, survival, and xenograft growth. Consistent with these results, EWI-2 levels were elevated in human malignant melanoma, but not in metastatic melanoma samples. Altered melanoma cell functions, caused by EWI-2 ablation, are almost entirely dependent on enhanced TRF-β1 signaling, and also require contributions from tetraspanin proteins CD9 and CD81. In melanoma cells lacking EWI-2, tetraspanins CD9 and CD81 enhance TRF-β1 signaling by facilitating TβR-2−TβR-1 receptor complex formation. When EWI-2 is present, CD9 and CD81 are diverted into EWI-2 complexes, and thus TRF-β1 signaling is inhibited.

2013-06-15 | GSE47978 | GEO

Pro-invasion metastasis drivers in early stage melanoma are oncogenes

Project description:Clinical and genomic evidence support the view that the metastatic potential of a primary tumor may be dictated by transforming events acquired early in the tumorigenic process. It has been proposed that the presence of such pro-metastatic events in early-stage tumors reflects their additional capability to function as oncogenes. Here, to test this ‘deterministic’ hypothesis and identify potential pro-metastasis oncogenes, we adopted a comparative oncogenomics-guided functional genetic screening strategy involving (i) global transcriptomic data from two genetically engineered mouse models of melanoma with contrasting metastatic potential, (ii) genomic and transcriptomic profiles of human primary and metastatic melanoma and (iii) an invasion screen in TERT-immortalized human melanocytes and melanoma cells in vitro as well as (iv) evidence of expression selection in human melanoma tissues. This integrated effort led to the identification of 6 genes that are both potently pro-invasive and oncogenic. Further, we show that one such pro-invasion oncogene, ACP5, can confer spontaneous metastasis in vivo, engages a key pathway governing metastasis and is prognostic in human primary melanomas. The tetracycline-inducible MET-driven mouse (iMet) model (Tyr-rtTA;Tet-Met;Ink4a/Arf-/-) was constructed similar to the previously described iHRAS* model (Tyr-rtTA;Tet-HRASV12G;Ink4a/Arf-/-). RNA from cutaneous melanomas derived from iMet (n=6) or iHRAS* (n=6) models were profiled on Affymetrix M430A_2 chips and resultant transcriptomes were compared to generate a phenotype-based (metastatic capable or not) differentially expressed gene list. Cross-species triangulation to human gene expression and copy number aberrations was based on ortholog mapping.

2011-07-11 | E-GEOD-29074 | biostudies-arrayexpress

Analysis of tetraspanin distribution on plasma and serum extracellular vesicles indicates that separate subpopulations carries CD9, CD63 and CD81

Project description:The ability to isolate extracellular vesicles (EVs) from blood is vital in the development of EVs as disease biomarkers. Both serum and plasma can be used, but few studies have compared these sources in terms of the quantity and type of EVs that are obtained. The aim of this study was therefore to determine the presence of different subpopulations of EVs in plasma and serum. Blood samples were collected from healthy subjects, from which plasma and serum were isolated in parallel. ACD-A or EDTA tubes were used for the collection of plasma, while serum was obtained in clot activator tubes. We previously developed a method utilising a combination of density cushion and size exclusion chromatography to isolate EVs from plasma with minimal contamination of lipoprotein particles. In the current study, we applied this method to both EDTA-plasma and serum. In addition, EVs were isolated by a combination of density cushion and density gradient or by bead immune capturing (anti-CD63, anti-CD9, and anti-CD81 beads). The subpopulations of EVs were analysed by nanoparticle tracking analysis, Western blot, single particle interferometric reflectance imaging sensing, conventional and nano flow cytometry, magnetic bead enzyme-linked immunosorbent assay, and mass spectrometry.This study shows that a larger number of CD9+ EVs are present in EDTA-plasma compared to ACD-plasma and serum, and the presence of CD41a on theses EVs suggests that they are released from platelets. Furthermore, only a small number of EVs in blood were double positive for CD63 and CD81. The CD63+ EVs were enriched in serum, while CD81+ vesicles were the rarest subpopulation in both plasma and serum. Together, these findings show that multiple subpopulations of EVs are present in blood including CD9+/CD41a+, CD9+/CD63+/CD41+, CD63+/CD41a+, CD63+/CD9+/CD81−, CD81+/CD9+/CD63−, and CD9+/CD63+/CD81+ and that their presence is dissimilar in EDTA-plasma, ACD-plasma and serum.

2022-05-20 | PXD026863 | Pride

Proteomic analysis of extracellular vesicle released by MCF7 cells in the absence of the tetraspanins CD9, CD81 or CD63

Project description:The tetraspanins CD9, CD81, and CD63 are among the most widely used markers of Extracellular Vesicles (EVs) and are also used to isolate the vesicles they decorate. If their function in EVs is largely unknown, they have been suggested to play a role in the sorting of protein cargos into EVs or to regulate the uptake of EVs by acceptor cells. Using different tetraspanin-deficient MCF7 breast cancer cell lines, we have shown that the absence of any of these 3 tetraspanins had a minimal impact on their protein composition, as analyzed by label-free quantitative mass spectrometry. However, the EVs released by cells deficient in both CD9 and CD81 showed a decrease level of CD9P-1/EWI-F and EWI-2 (encoded by the genes PTGFRN and IGSF8 respectively), which are two well-characterized CD9 and CD81 molecular partners.

2023-08-03 | PXD042940 | Pride

Transcription profiling of rat PC12 cells treated with cholecystokinin for 2, 4, 8, and 16 hours

Project description:1 x 106 PC12-CCK-2R cells/100 mm or 1 x 106 PC12 cells/100 mm were seeded in DMEM containing 0.5% serum for 2 days before cells were untreated or treated with 200 nM CCK-8S for 2, 4, 8, and 16 hours. Total cellular RNA was isolated. Three independent series containing RNA from four 100 mm petri dishes were pooled to minimize differences in cell cultures and treatments.

2007-11-09 | E-MEXP-1169 | biostudies-arrayexpress

Cell cannibalism, a cell-death process driven by the Transforming Growth Factor-M-NM-2 and the Nuclear Protein 1, opposes to metastasis in pancreatic cancer

Project description:Pancreatic adenocarcinoma (PDAC) is an extremely deadly disease for which all treatments available have failed to improve life expectancy significantly. This may be explained by the high metastatic potential of PDAC cells, which results from their physiological dedifferentiation towards a mesenchymal phenotype. Some PDAC present cell-in-cell structures but their origin and significance is currently unknown. We show here that cell-incells form after cell cannibalism. We found PDAC patients whose tumors display cell cannibalism develop less metastasis than those without. In vitro, cell cannibalism was enhanced by the TGFM-NM-2 and repressed by the Nuclear protein (Nupr)1, and was coupled to a defective epithelial-to-mesenchymal transition of PDAC cells. Cannibalism ends with death of PDAC cells, consistent with a metastasis suppressor role for this phenomenon. Hence, our data indicates a protective role for cell cannibalism in PDAC and identifies Nupr1 and TGFM-NM-2 as molecular regulators of this process. Cell culture and culture reagents. Panc-1 cells were cultured in Glutamax-containing DMEM(Invitrogen) and BxPC3 in RPMI (Invitrogen), both supplemented with 10% FBS (PAA Laboratories). All cells were maintained at 37M-BM-0C, 5% CO2, H2O saturated. TGFM-NM-21 (Peprotech) was used at 10 ng/ml .siRNA-mediated gene silencing. Panc-1 cells were seeded in 6-wells plates to reach 30% to 50% confluence. Twenty-four hours later, a mix containing 2.2 pmoles of siRNA and 8 M-NM-<l of the transfection reagent INTERFERIN (Polyplus Transfection) was added to the culture medium according to manufacturerM-bM-^@M-^Ys instructions. Panc-1 Nupr1-depleted cells (sip8), and controls cells (siCtrl) were further incubated for 7 or 24 hrs before TGFM-NM-21 treatment without change of medium.

2012-06-17 | E-GEOD-38772 | biostudies-arrayexpress

CD9-HPLC-IAC Isolation of Serum Extracellular Vesicles for Proteomic Analysis

Project description:We developed a column-based CD9 antibody-immobilized HPLC immunoaffinity (CD9-HPLC-IAC) technology for EV isolation from a microliter-scale of serum for downstream proteomic analysis. The CD9-HPLC-IAC method achieved EV isolation from 40 μL of serum in 30 min with a yield of 8.0×109 EVs. Proteomic analysis showed that the common exosomal markers such as CD63, CD81, CD82, Alix, and TSG101 were all identified in EVs. Statistical analysis of EV protein content showed that the top 10 serum proteins in EVs was significantly decreased by using the CD9-HPLC-IAC method compared to the ultracentrifugation (UC) (p=0.001) and size exclusion chromatography (SEC) (p=0.009), and apolipoproteins significantly reduced 4.8-fold compared to the SEC method (p<0.001). The result demonstrated the potential of the CD9-HPLC-IAC method for efficient isolation and proteomic characterization of EVs from a micro-scale volume of serum.

2022-10-14 | PXD027025 | Pride

Probing off-target effect of LMNA siRNA and pro-siRNA in HeLa-d1EGFP cell line

Project description:We have develped a novel method of making siRNAs (named pro-siRNA for prokaryotic siRNA). To evaluate off-targeting of pro-siRNA, we compared mRNA expression profile of HeLa-d1EGFP cells transfected with 4 nM LMNA siRNAs and pro-siRNAs by microarray. We used microarray to study off-target effect of siRNAs in HeLa-d1EGFP cell line. After transfection of siRNAs for 24 hrs, RNA were extracted using Trizol. RNA samples were sent to Microarray Core at Dana-Farber Cancer Institute (http://macf-web.dfci.harvard.edu/index.php?option=com_frontpage&Itemid=1) to be probed using Human Gene 1.0 ST (Affymetrix).

2013-02-06 | E-GEOD-44105 | biostudies-arrayexpress

An Integrated Approach to Uncover Drivers of Cancer

Project description:We developed a computational framework that integrates chromosomal copy number and gene expression data for detecting aberrations that promote cancer progression. We demonstrate the utility of this framework using a melanoma dataset. Our analysis correctly identified known drivers of melanoma and predicted multiple novel tumor dependencies. Two dependencies, TBC1D16 and RAB27A, confirmed empirically, suggest that abnormal regulation of protein trafficking contributes to proliferation in melanoma. Together, these results demonstrate the ability of integrative Bayesian approaches to identify novel candidate drivers with biological, and possibly therapeutic, importance in cancer. Effects of knockdown of two genes -TBC1D16 and RAB27A - were tested on four cell lines each, each of them with two different hairpins. As a control, we used a hairping targeting GFP. shGFP experiments were done in biological duplicates or more. The second WM1976-shGFP sample was identified as an outlier by a PCA analysis and was excluded from our analysis.

2010-12-01 | E-GEOD-23884 | biostudies-arrayexpress

Expression data of CD9 positive germ cells from young and aged Sprague Dawley germ cell specific GFP rats

Project description:Male fertility and testis function changes with age and so it was sought to determine if these changes are accompanied by changes in gene expression in the spermatogonial cells at the foundation of spermatogenesis A full genome microarray was used to determine if distinct pathways of genes were altered in expression in CD9-positive germ cells with age Testes from young (4 months) and aged (21 months) Sprague Dawley rats were subjected to dissociation to isolate a singel cell suspension of germ cells. These cells were used to isolate CD9 positive spermatogonial cells. RNA was isolated from these cells for hybridization on agilent miroarrays.

2013-12-05 | E-GEOD-50143 | biostudies-arrayexpress

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