A5050926591- Monoclonal and Polyclonal Antibodies Research
- Radiopharmaceutical Chemistry and Applications
- RNA and protein synthesis mechanisms
- Lung Cancer Treatments and Mutations
- RNA Research and Splicing
- RNA modifications and cancer
- Cancer-related gene regulation
- Axon Guidance and Neuronal Signaling
- Computational Drug Discovery Methods
- Hippo pathway signaling and YAP/TAZ
- HER2/EGFR in Cancer Research
- Receptor Mechanisms and Signaling
- Risk and Safety Analysis
- Zebrafish Biomedical Research Applications
- Biomarkers in Disease Mechanisms
Case Western Reserve University
2021-2023
University School
2021-2023
MetroHealth Medical Center
2021-2023
Case Comprehensive Cancer Center
2021-2023
MetroHealth
2021-2023
University Hospitals Cleveland Medical Center
2021
Ephrin type-A receptor 2 (EphA2) is a tyrosine kinase that initiates both ligand-dependent tumor-suppressive and ligand-independent oncogenic signaling. We used time-resolved, live-cell fluorescence spectroscopy to show the ligand-free EphA2 assembles into multimers driven by two types of intermolecular interactions in ectodomain. The first type entails extended symmetric required for ligand-induced clustering signaling inhibits activity extracellular signal–regulated (ERK) protein B (AKT)...
Accumulating analyses of pro-oncogenic molecular mechanisms triggered a rapid development targeted cancer therapies. Although many these treatments produce impressive initial responses, eventual resistance onset is practically unavoidable. One the main approaches for preventing this refractory condition relies on implementation combination This includes dual-specificity reagents that affect both their targets with high level selectivity. Unfortunately, selection target combinations often...
ABSTRACT The EphA2 receptor tyrosine kinase mediates ligand-induced canonical signaling associated with tumor suppression and ligand-independent noncanonical implicated in progression. Using time-resolved fluorescence spectroscopy live cells, we find that unliganded receptors pre-assemble into multimers, which is mediated by two symmetric one asymmetric interfaces the ectodomain. Upon ligand binding, are further assemble large clusters also requires three interfaces. Functionally, disrupting...
EphA2, a member of Eph family receptor tyrosine kinases (RTKs), is overexpressed in multiple types solid human tumors, particularly at the late stages. However, whether and how it drives specific malignant processes remain elusive. We report that EphA2 elevated during prostate cancer (PCa) progression syngeneic murine models. Interestingly, metastatic PCa specimens from two Rapid Autopsy Programs showed selective overexpression metastasis to bone, but not lymph nodes or viscera. Serine 897...
<p>Fig. S4. A. Heatmap of the shRNA screen hits that are enriched in top 15 GO processesgenerated using GSEA software. B. Gene Set Enrichment Analysis plots GOprocess for data produced by software used to generate heatmap inA.</p>
<p>Fig. S6. EPHA2, c-MET and EGFR levels in human tumors.</p>
<p>Fig. S4. A. Heatmap of the shRNA screen hits that are enriched in top 15 GO processesgenerated using GSEA software. B. Gene Set Enrichment Analysis plots GOprocess for data produced by software used to generate heatmap inA.</p>
<p>Fig. S2. A. Heatmap of the differentially expressed phosphorylated proteins that are enriched inthe top 15 gene ontology (GO) processes generated using GSEA software. B. Gene SetEnrichment Analysis plots GO for expressedphosphorylated data produced by software used to generate heatmap in A.</p>
<p>Fig. S3. A. Correlation cluster for both the replicates and different timepoints of screeningdata. B. Fold-change distribution from normalized shRNA intensity αEPHA2-Condand cIgG-Tr cells at time points. C. Precision-recall curves after applying BAGELalgorithm to screening data. F measure provided in inset represents harmonic mean ofprecision & recall screen.</p>
<p>Fig. S5. A. Heatmap of the BioID hits that are enriched in top 15 GO processes based onGSEA software. B. Gene Set Enrichment Analysis plots process for BioIDdata produced by GSEA software used to generate heatmap A.</p>
<p>-Supplementary Materials</p>
<p>Fig. S1. The amino acid sequence of EPHA2 extracellular portion composed ligand bindingdomain followed by sushi-like domain and two sequential fibronectin-like domains is highlyconserved among mammals.</p>
<div>AbstractPurpose:<p>Accumulating analyses of pro-oncogenic molecular mechanisms triggered a rapid development targeted cancer therapies. Although many these treatments produce impressive initial responses, eventual resistance onset is practically unavoidable. One the main approaches for preventing this refractory condition relies on implementation combination This includes dual-specificity reagents that affect both their targets with high level selectivity. Unfortunately,...
<p>Fig. S6. EPHA2, c-MET and EGFR levels in human tumors.</p>