Dataset Information

Data on quantification of signaling pathways activated by KIT and PDGFRA mutants.

ABSTRACT: The present data are related to the article entitled "Insights into ligand stimulation effects on gastro-intestinal stromal tumors signaling" (C. Bahlawane, M. Schmitz, E. Letellier, K. Arumugam, N. Nicot, P.V. Nazarov, S. Haan, 2016) [1]. Constitutive and ligand-derived signaling pathways mediated by KIT and PDGFRA mutated proteins found in gastrointestinal stromal tumors (GIST) were compared. Expression of mutant proteins was induced by doxycycline in an isogenic background (Hek293 cells). Kit was identified by FACS at the cell surface and found to be quickly degraded or internalized upon SCF stimulation for both Kit Wild type and Kit mutant counterparts. Investigation of the main activated pathways in GIST unraveled a new feature specific for oncogenic KIT mutants, namely their ability to be further activated by Kit ligand, the stem cell factor (scf). We were also able to identify the MAPK pathway as the most prominent target for a common inhibition of PDGFRA and KIT oncogenic signaling. Western blotting and micro-array analysis were applied to analyze the capacities of the mutant to induce an effective STATs response. Among all Kit mutants, only Kit Ex11 deletion mutant was able to elicit an effective STATs response whereas all PDGFRA were able to do so.

SUBMITTER: Bahlawane C

PROVIDER: S-EPMC5107687 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Data on quantification of signaling pathways activated by KIT and PDGFRA mutants.

Bahlawane Christelle C Schmitz Martine M Letellier Elisabeth E Arumugam Karthik K Nicot Nathalie N Nazarov Petr V PV Haan Serge S

Data in brief 20161102

The present data are related to the article entitled "Insights into ligand stimulation effects on gastro-intestinal stromal tumors signaling" (C. Bahlawane, M. Schmitz, E. Letellier, K. Arumugam, N. Nicot, P.V. Nazarov, S. Haan, 2016) [1]. Constitutive and ligand-derived signaling pathways mediated by KIT and PDGFRA mutated proteins found in gastrointestinal stromal tumors (GIST) were compared. Expression of mutant proteins was induced by doxycycline in an isogenic background (Hek293 cells). Kit ...[more]

PMID: 27872880

Similar Datasets

Project description:Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor in the gastrointestinal tract. The present study aimed to identify the potential candidate biomarkers that may be involved in the pathogenesis and progression of v?kit Hardy?Zuckerman 4 feline sarcoma viral oncogene homolog (KIT)/platelet?derived growth factor receptor ? (PDGFRA) wild?type GISTs. A joint bioinformatics analysis was performed to identify the differentially expressed genes (DEGs) in wild?type GIST samples compared with KIT/PDGFRA mutant GIST samples. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs was conducted using Database for Annotation, Visualization and Integrated Discovery and KEGG Orthology?Based Annotation System (KOBAS) online tools, respectively. Protein?protein interaction (PPI) networks of the DEGs were constructed using Search Tool for the Retrieval of Interacting Genes online tool and Cytoscape, and divided into sub?networks using the Molecular Complex Detection (MCODE) plug?in. Furthermore, enrichment analysis of DEGs in the modules was analyzed with KOBAS. In total, 546 DEGs were identified, including 238 upregulated genes primarily enriched in 'cell adhesion', 'biological adhesion', 'cell?cell signaling', 'PI3K?Akt signaling pathway' and 'ECM?receptor interaction', while the 308 downregulated genes were predominantly involved in 'inflammatory response', 'sterol metabolic process' and 'fatty acid metabolic process', 'small GTPase mediated signal transduction', 'cAMP signaling pathway' and 'proteoglycans in cancer'. A total of 25 hub genes were obtained and four modules were mined from the PPI network, and sub?networks also revealed these genes were primarily involved in significant pathways, including 'PI3K?Akt signaling pathway', 'proteoglycans in cancer', 'pathways in cancer', 'Rap1 signaling pathway', 'ECM?receptor interaction', 'phospholipase D signaling pathway', 'ras signaling pathway' and 'cGMP?PKG signaling pathway'. These results suggested that several key hub DEGs may serve as potential candidate biomarkers for wild?type GISTs, including phosphatidylinositol?4,5?bisphosphate 3?kinase, catalytic subunit ?, insulin like growth factor 1 receptor, hepatocyte growth factor, thrombospondin 1, Erb?B2 receptor tyrosine kinase 2 and matrix metallopeptidase 2. However, further experiments are required to confirm these results.

Dataset Information

Data on quantification of signaling pathways activated by KIT and PDGFRA mutants.

Publications

Data on quantification of signaling pathways activated by KIT and PDGFRA mutants.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets