Signaling networks assembled by oncogenic EGFR and c-Met
| العنوان: | Signaling networks assembled by oncogenic EGFR and c-Met |
|---|---|
| المؤلفون: | Matthew P. Stokes, Anthony Possemato, Randall K. Wetzel, Jeffrey Mitchell, Michael J. Comb, Julie Nardone, Kimberly Lee, Judit Villén, Joan MacNeill, Roberto D. Polakiewicz, Jon M. Kornhauser, Gregory Innocenti, John Rush, Ailan Guo, Klarisa Rikova, Yi Wang, Steven P. Gygi |
| المصدر: | Proceedings of the National Academy of Sciences. 105:692-697 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Proteomics, Lung Neoplasms, C-Met, Models, Biological, Receptor tyrosine kinase, chemistry.chemical_compound, Gefitinib, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, medicine, Humans, Neoplasm Metastasis, Phosphotyrosine, Protein Kinase Inhibitors, EGFR inhibitors, Multidisciplinary, biology, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-met, Biological Sciences, ErbB Receptors, Gene Expression Regulation, Neoplastic, chemistry, Drug Resistance, Neoplasm, Quinazolines, biology.protein, Cancer research, Cyclin-dependent kinase 8, Signal transduction, Tyrosine kinase, Signal Transduction, medicine.drug |
| الوصف: | A major question regarding the sensitivity of solid tumors to targeted kinase inhibitors is why some tumors respond and others do not. The observation that many tumors express EGF receptor (EGFR), yet only a small subset with EGFR-activating mutations respond clinically to EGFR inhibitors (EGFRIs), suggests that responsive tumors uniquely depend on EGFR signaling for their survival. The nature of this dependence is not understood. Here, we investigate dependence on EGFR signaling by comparing non-small-cell lung cancer cell lines driven by EGFR-activating mutations and genomic amplifications using a global proteomic analysis of phospho-tyrosine signaling. We identify an extensive receptor tyrosine kinase signaling network established in cells expressing mutated and activated EGFR or expressing amplified c-Met. We show that in drug sensitive cells the targeted tyrosine kinase drives other RTKs and an extensive network of downstream signaling that collapse with drug treatment. Comparison of the signaling networks in EGFR and c-Met-dependent cells identify a “core network” of ≈50 proteins that participate in pathways mediating drug response. |
| تدمد: | 1091-6490 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6085f51aef25b85bb2a1eb36e7b8da74Test https://doi.org/10.1073/pnas.0707270105Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6085f51aef25b85bb2a1eb36e7b8da74 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
|---|