Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

18 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Proteomic profiling by array of tyrosine kinase activity in metastatic malignant melanoma from human tissue specimens

ABSTRACT: Tyrosine kinase activity profiling of metatstatic malignant melanoma and normal skin tissue samples was performed using peptide kinase arrays. All samples were run in triplicates with and withouth inhbitor PLX4032 and Sutent Malate in order to identify how tyrosine kinases responds to kinase inhibitor treatment, ex vivo.

ORGANISM(S): Homo sapiens

SUBMITTER: Andliena Tahiri

PROVIDER: E-MTAB-1245 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Publications

Differential inhibition of ex-vivo tumor kinase activity by vemurafenib in BRAF(V600E) and BRAF wild-type metastatic malignant melanoma.

Tahiri Andliena A Røe Kathrine K Ree Anne H AH de Wijn Rik R Risberg Karianne K Busch Christian C Lønning Per E PE Kristensen Vessela V Geisler Jürgen J

PloS one 20130830 8

<h4>Background</h4>Treatment of metastatic malignant melanoma patients harboring BRAF(V600E) has improved drastically after the discovery of the BRAF inhibitor, vemurafenib. However, drug resistance is a recurring problem, and prognoses are still very bad for patients harboring BRAF wild-type. Better markers for targeted therapy are therefore urgently needed.<h4>Methodology</h4>In this study, we assessed the individual kinase activity profiles in 26 tumor samples obtained from patients with meta ...[more]

PMID: 24023633

Similar Datasets

Kinase activity profiling of human locally advanced rectal cancer samples

Project description:Locally advanced rectal cancer characterized by multiplex kinase activity profiling

2010-08-05 | E-TABM-913 | biostudies-arrayexpress

Proteomic profiling of colorectal cancer cell culture samples treated with apoptosis- and mTOR inhibitors under normoxia and hypoxia

Project description:To examine changes in tyrosine kinase activity in colorectal cancer cell culture samples treated with apoptosis inhibitors or/and mTOR inhibitors, under normoxic or/and hypoxic experimental conditions.

2016-06-15 | E-MTAB-3870 | biostudies-arrayexpress

Proteomic profiling of human monocytes stimulated in vitro with N. meningitidis

Project description:Meningococcal sepsis is an overwhelming form of the sepsis syndrome which may cause mortality within 12-24 hours in previously healthy children and adults, where the causative infectious agent is N. meningitidis, an obligate human pathogen. The genomic changes induced by N. meningitidis are modulated by the anti-inflammatory cytokine interleukin-10 (IL-10), which is present in large quantities in plasma from patients with meningococcal sepsis. This present study investigated kinase activities in human monocytes stimulated by N. meningitidis and IL-10. The first aim was to identify array peptides that could indicate which signaling pathways were activated or inhibited by the host response to the meningococci. The second aim was to detect whether IL-10 affected N. meningitidis-nduced phosphorylation of array peptides, in order to identify potential targets of the IL-10 anti-inflammatory response. We approached this using a strategy where elutriation-purified human monocytes are stimulated in vitro with N. meningitidis and IL-10, with concentrations corresponding to previously measured levels in patients with fulminant meningococcal septicemia. This work examined activation or inhibition of signaling pathways mediated by tyrosine kinases when purified human monocytes are in vitro incubated with N. meningitidis in the presence or absence of IL-10.

2017-12-15 | E-MTAB-4795 | biostudies-arrayexpress

Hypoxic tumor kinase signaling mediated by STAT5A in development of castration-resistant prostate cancer

Project description:To examine changes in tyrosine kinase activity in prostate cancer tumors developing resistance to androgen deprivation therapy and to compare these to changes in tyrosine kinase activity occuring in cell lines exposed to oxygen deficiency (hypoxia)

2013-04-15 | E-MTAB-1572 | biostudies-arrayexpress

HDAC8 regulates escape from BRAF inhibitor therapy in Melanoma: IMAC Phosphoproteomics

Project description:Melanoma cells are highly plastic and have the ability to switch to a dedifferentiated, invasive phenotype in response to multiple stimuli. Here, we show that exposure of melanoma cell lines and patient specimens to multiple stresses including BRAF-MEK inhibitor therapy, hypoxia and UV-irradiation leads to an increase in histone deacetylase 8 (HDAC8) expression/activity, and in turn, the adoption of a drug-resistant, invasive phenotype. Systems level analyses using mass spectrometry-based phosphoproteomics implicated HDAC8 in the regulation of MAPK and AP-1 signaling pathways. Introduction of HDAC8 into drug-naïve melanoma cells conveyed resistance both in vitro and in in vivo xenograft models. HDAC8-mediated BRAF inhibitor resistance was mediated via receptor tyrosine kinase (RTK) activation leading to Ras/CRAF/MEK/ERK signaling. Although HDACs primarily function at the histone level, they also regulate signaling through the modulation of non-histone substrates. In line with this, HDAC8 introduction decreased the acetylation of c-Jun, increasing its transcriptional activity and enriching for an AP-1 gene signature. Mutation of the putative c-Jun acetylation site at lysine residue 273 reduced the transcriptional activation of c-Jun in melanoma cells and conveyed resistance to BRAF inhibition through increased RTK expression and enhanced MAPK pathway activity. In vivo xenograft studies confirmed the key role of HDAC8 in therapeutic adaptation, with both non-selective and HDAC8-specific inhibitors enhancing the durability of response to BRAF inhibitor therapy. Our studies demonstrate that HDAC8-specific inhibitors could represent an excellent strategy to limit the adaptation of melanoma cells to multiple stresses and therapeutic interventions, including BRAF-MEK inhibitor combinations.

2020-07-07 | PXD012813 | Pride

Identifying Kinase Substrates via a Heavy ATP Kinase Assay and Quantitative Mass Spectrometry

Project description:Mass spectrometry‐based in vitro kinase screens play an essential role in the discovery of kinase substrates, however, many suffer from biological and technical noise or necessitate genetically‐altered enzymecofactor systems. We describe a method that combines stable γ‐[18O2]‐ATP with classical in vitro kinase assays within a contemporary quantitative proteomic workflow. Our approach improved detection of known substrates of the non‐receptor tyrosine kinase ABL1; and identified potential, new in vitro substrates.

2018-10-17 | PXD002133 | Pride

Non-canonical EphA2 signaling is a driver of tumor-endothelial cell interactions and metastatic dissemination in BRAF inhibitor resistant melanoma

Project description:Acquired BRAF/MEK inhibitor resistance in melanoma results in a new transcriptional state associated with increased risk of metastasis. Here, we identified non-canonical EphA2 signaling as a driver of the resistance-associated metastatic state. We used mass spectrometry-based proteomic and phenotypic assays to demonstrate that the expression of active non-canonical EphA2-S897E in melanoma cells led to a mesenchymal-to-amoeboid transition (MAT) driven by Cdc42 activation. The induction of MAT promoted melanoma cell invasion, survival under shear stress, adhesion to endothelial cells under continuous flow conditions, increased permeability of endothelial cell monolayers and stimulated melanoma transendothelial cell migration. In vivo, melanoma cells expressing EphA2-S897E or active Cdc42 showed superior lung retention following tail-vain injection. Analysis of BRAF inhibitor-sensitive and -resistant melanoma cells demonstrated resistance to be associated with an MAT switch, upregulation of Cdc42 activity, increased invasion, and transendothelial migration. The drug resistant metastatic state was dependent upon histone deacetylase 8 (HDAC8) activity. Silencing of HDAC8 lead to inhibition of EphA2 and AKT phosphorylation, reduced invasion and impaired melanoma cell-endothelial cell interactions. In summary, we have demonstrated that the metastatic state associated with acquired BRAF inhibitor resistance is dependent on non-canonical EphA2 signaling, leading to increased melanoma-endothelial cell interactions and enhanced tumor dissemination.

2020-11-18 | PXD020250 | Pride

HDAC8 regulates escape from BRAF inhibitor therapy in Melanoma: Phosphotyrosine Profiling

2020-07-07 | PXD012812 | Pride

De novo BCR-ABL linear kinase motifs revealed by phosphoproteomics in yeast

Project description:Protein tyrosine phosphorylation (pY) is central to many cellular signaling pathways. Deregulation of pY can lead to malignancies such as leukemia. Thus, assigning kinase-substrate relations is imperative to understand disease alterations. However, such efforts are complicated by kinase redundancy, overlapping specificity and magnitude differences in enzymatic activity. BCR/ABL, the predominant oncogene in leukemia, drives malignant transformation by deregulated tyrosine kinase activity. In this study, phosphorylation activity and specificity of human ABL1 and BCR/ABL have been examined in yeast by state-of-the-art phosphoproteomics. Linear sequence motif scores were generated and used for cross-kingdom (fungi to metazoa) phosphorylation analysis. Phosphoproteomic analysis of ABL1 and BCR/ABL yielded a high-confidence pY-dataset of 1186 peptides covering 1127 sites on 821 proteins. Motif scores generated from this dataset allow for examination of ABL1 and BCR/ABL kinase activity in human cell lines, and clearly identified BCR/ABL p210 in the chronic myeloid leukemia cell line K562. This cross-kingdom approach offers valuable insights into the human phosphoproteome.

2023-07-20 | PXD038551 | Pride

Transcription profiling by array of mouse dendritic cells which were pulsed with apoptotic bodies from NIT-1 cells

Project description:We have been interested whether peripheral tolerance can be restored by vaccination with antigen-presenting cells (APCs) loaded with apoptotic bodies. Dendritic cells (DCs) are powerful APCs that have a critical role in the initiation and progression of autoimmunity. We previously demonstrated that DCs loaded with apoptotic islet cells prevents experimental type 1 diabetes (T1D), an autoimmune disease caused by beta-cell destruction. The goal of this study is to characterize the molecular changes on gene expression -transcriptome- occurring in these DCs pulsed with apoptotic bodies. Cells from four different genetically identical NOD (Non-Obese Diabetic) mice were used to obtain DCs. DCs were loaded with apoptotic bodies from NIT-1 cell line (insulinoma from NOD mice). Unloaded DCs were used as control in four paired experiments. Moreover, transcriptome from NIT-1 apoptotic bodies was determined. Mouse Gene 1.0 ST Arrays from Affymetrix (28,853 genes) were hybridized and genes with a p-value <= 0.002, adjusted p-value <= 0.08 and fold change (FC) >= 1.38 were considered upregulated, and genes with FC <= -1.37 were considered downregulated. Results demonstrate that apoptotic cells engulfment promotes molecular changes in DCs towards tolerogenic features. Gene expression profile of DCs from NOD mice that captured NIT-1 apoptotic bodies showed a downregulation of genes involved in antigen presentation and differential expression of cytokine, chemokine, natural immunity and immunoregulation genes together with the presence of specific transcripts for islet autoantigens. Molecular changes of DCs caused by the uptake of apoptotic bodies are key factors to induce antigen-specific peripheral tolerance.

2013-05-22 | E-MEXP-3374 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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