Effect of DNA damage on ligand stimulated EGFR signaling pathways
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA759859 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15700035.fastq.gz | Fastqsanger.gz | |||
| SRR15700036.fastq.gz | Fastqsanger.gz | |||
| SRR15700037.fastq.gz | Fastqsanger.gz | |||
| SRR15700038.fastq.gz | Fastqsanger.gz | |||
| SRR15700039.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:We examined the cellular response of primary normal cells to EGFR stimulation under normal and DNA damage conditions.
2022-04-19 | GSE183269 | GEO
Project description:Pancreatic ribonuclease (RNase) is a secreted enzyme critical for host defense. We discover an intrinsic RNase function, serving as a ligand for epidermal growth factor receptor (EGFR), a member of receptor tyrosine kinase (RTK), in pancreatic ductal adenocarcinoma (PDAC). The closely related bovine RNase A and human RNase 5 (angiogenin/ANG) can trigger oncogenic transformation independently of their catalytic activities via direct association with EGFR. Notably, high plasma ANG level in PDAC patients is positively associated with response to EGFR inhibitor erlotinib treatment. These results identify a previously unrecognized role of ANG as a serum biomarker, which may be used to stratify patients for EGFR-targeted therapies, and offer insights into the ligand-receptor relationship between RNase and RTK families.
2018-04-18 | GSE109427 | GEO
Project description:Macrophages in the tumor microenvironment have a substantial impact on tumor progression. Depending on the signaling environment in the tumor, macrophages can either support or constrain tumor progression. It is therefore of therapeutic interest to identify the tumor-derived factors that control macrophage education. With this aim, we correlated the expression of A Disintegrin and Metalloproteinase (ADAM) proteases, which are key mediators of cell-cell signaling, to the expression of protumorigenic macrophage markers in human cancer cohorts. We identified ADAM17, a sheddase upregulated in many cancer types, as a protein of interest. Depletion of ADAM17 in cancer cell lines reduced the expression of several protumorigenic markers in neighboring macrophages in vitro as well as in mouse models. Moreover, ADAM17–/– educated macrophages demonstrated a reduced ability to induce cancer cell invasion. Using mass spectrometry–based proteomics and ELISA, we identified HB-EGF and AREG, shed by ADAM17 in the cancer cells, as the implicated molecular mediators of macrophage education. Additionally, RNA-Seq and ELISA experiments revealed that ADAM17-dependent HB-EGF ligand release induced the expression and secretion of CXCL chemokines in macrophages, which in turn stimulated cancer cell invasion. In conclusion, we provide evidence that ADAM17 mediates a paracrine EGFR-ligand-chemokine feedback loop, whereby cancer cells hijack macrophages to promote tumor progression.
2022-09-02 | GSE212316 | GEO
Project description:Ligand binding to the EGF receptor (EGFR) initiates signal transduction and endocytosis of the receptor. The mechanisms of endocytosis and regulation of signaling by endocytosis are poorly understood. Here, we combined peroxidase-catalyzed proximity labeling, isobaric peptide tagging and quantitative mass-spectrometry to define the dynamics of the proximity proteome of EGFR in response to ligand activation. Using this approach, we identified a network of signaling proteins, which remain associated with the receptor during its endocytosis and trafficking through the endosomal system. We showed that Trk-fused gene (TFG), a protein known to function at the endoplasmic reticulum exit sites, was enriched early/sorting endosome proximity proteome of EGFR and localized in early an sorting endosomes, and demonstrated that TFG regulates endosomal sorting of EGFR. This study provides a large-scale resource of time-dependent nanoscale environment of activated EGFR, thus opening avenues to discovering new regulatory mechanisms of membrane trafficking of receptor tyrosine kinases. EGFR-APEX2 Experiment Datasets: TMT 1-3: HEK293T cells (0, 1, 10, 30 and 60 minutes EGF treatment) TMT 4: HCT116 cells (0, 2, 4, 6 , 8 and 10 minutes EGF treatment) TMT 5: HEK293T cells (0, 2, 4, 6 , 8 and 10 minutes EGF treatment) TMT 6: HEK293T cells (0 and 10 minutes EGF treatment) TMT 7: HCT116 cells (0 and 10 minutes EGF treatment)
2022-06-04 | PXD030072 | Pride
Project description:ADAM17-mediated EGFR ligand shedding directs macrophage-promoted cancer cell invasion
| PRJNA875032 | ENA
Project description:Selection of activating EGFR mutations from randomly mutated EGFR libraries
| PRJEB49811 | ENA
Project description:Co-amplification of EGFR and EGFRvIII, a tumor-specific truncation mutant of EGFR, represent hallmark genetic lesions in glioblastoma. We report that EGFR and EGFRvIII stimulate the innate immune defense receptor Toll-like Receptor 2 (TLR2); and that knockdown of TLR2 led to a dramatic survival advantage in glioblastoma xenografts. EGFR and EGFRvIII activated TLR2 in a ligand-independent manner, promoting tumor growth and immune evasion. We show that EGFR and EGFRvIII cooperate to activate the Rho-associated protein kinase ROCK2, modulating malignant progression both by activating TLR2 and WNT signaling, and through remodeling the tumor microenvironment.
2024-11-26 | PXD034586 | Pride
Project description:The highly conserved Epidermal Growth Factor-receptor (Egfr) pathway is required in all animals for normal development and homeostasis; consequently, aberrant Egfr signaling is implicated in a number of diseases. Genetic analysis of Drosophila melanogaster Egfr has contributed significantly to understanding this conserved pathway and has led to the discovery of new components and targets. Here we used microarray analysis of Drosophila third instar wing discs, in which Egfr signaling was perturbed, to identify new Egfr-responsive genes. Upregulated transcripts included five known targets suggesting the approach was valid. We investigated the function of 29 previously uncharacterized genes, which had pronounced responses. The Egfr pathway is important for wing-vein patterning and using reverse genetic analysis we identified five genes that showed venation defects. Three of these genes are expressed in vein primordia and all showed transcriptional changes in response to altered Egfr activity consistent with being targets of the pathway. Genetic interactions with Egfr further linked two of the genes, Sulfated (Sulf1), an endosulfatase gene, and CG4096, an ADAMTS (A Disintegrin And Metalloproteinase with ThromboSpondin motifs) gene, to the pathway. Sulf1 showed a strong genetic interaction with the neuregulin-like ligand vein (vn) and may influence binding of Vn to heparan-sulfated proteoglycans (HSPGs). Genetic evidence also shows that CG4096 functions by modulating activity of the Egfr ligands. The substrate(s) and how ligand activity is affected are unknown, but interestingly vertebrate EGF ligands are regulated by a related ADAMTS protein. We conclude Sulf1 and CG4096 are negative feedback regulators of Egfr signaling that function in the extracellular space to influence ligand activity. 3 replicates each of wing disc samples in which EGFR dominant negative (EGFR-DN) or EGFR activated (EGFR-TOP) transgenes were expressed with the 71B-Gal4 driver.
2012-01-06 | E-GEOD-34872 | biostudies-arrayexpress
Project description:Our research data suggest that almost all basal-like tumors have an EGFR-activation profile, however, few may respond to the direct inhibition of EGFR due to ligand independent activation of the EGFR-RAS-MEK pathway via CRYAB or KRAS function. Thus, for those tumors that show a ligand independent EGFR-activation profile, alternative strategies that target downstream components like MEK may prove to be viable alternatives. Keywords: reference x sample
2007-08-20 | GSE6128 | GEO
Project description:Profiling of MCF-7 cell lines stably overexpressing constitutively active Raf-1, constitutively active MEK, constitutively active c-erbB-2, or ligand-activatable EGFR as models of overexpressed growth factor signaling, as well as control vector transfected cells (coMCF-7) and control vector transfected cells long-term adapted for estrogen-independent growth (coMCF-7/lt-E2). Keywords: Cell Line Comparison
2006-04-06 | GSE3542 | GEO