Soluble monomeric EphrinA1 is released from tumor cells and is a functional ligand for the EphA2 receptor
| العنوان: | Soluble monomeric EphrinA1 is released from tumor cells and is a functional ligand for the EphA2 receptor |
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| المؤلفون: | Waldemar Debinski, S.L. Ringler, Cp P. Turner, Dm M. Gibo, Enzo Palma, J. Wykosky |
| المصدر: | Oncogene. 27:7260-7273 |
| بيانات النشر: | Springer Science and Business Media LLC, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Cancer Research, media_common.quotation_subject, Biology, Ligands, Transfection, Cell morphology, Article, Biophysical Phenomena, Paracrine signalling, Growth factor receptor, Downregulation and upregulation, Cell Line, Tumor, Genetics, Humans, Receptor, Internalization, Molecular Biology, media_common, Receptor, EphA2, Ephrin-A1, Juxtacrine signalling, Cell biology, Gene Expression Regulation, Solubility, Glioblastoma |
| الوصف: | The ephrinA1 ligand exerts antioncogenic effects in tumor cells through activation and downregulation of the EphA2 receptor and has been described as a membrane-anchored protein requiring clustering for function. However, while investigating the ephrinA1/EphA2 system in the pathobiology of glioblastoma multiforme (GBM), we uncovered that ephrinA1 is released from GBM and breast adenocarcinoma cells as a soluble, monomeric protein and is a functional form of the ligand in this state. Conditioned media containing a soluble monomer of ephrinA1 caused EphA2 internalization and downregulation, dramatic alteration of cell morphology and suppression of the Ras-MAPK pathway. Moreover, soluble monomeric ephrinA1 was functional in a physiological context, eliciting collapse of embryonic neuronal growth cones. We also found that ephrinA1 is cleaved from the plasma membrane of GBM cells, an event which involves the action of a metalloprotease. Thus, the ephrinA1 ligand can, indeed, function as a soluble monomer and may act in a paracrine manner on the EphA2 receptor without the need for juxtacrine interactions. These findings have important implications for further deciphering the function of these proteins in pathology and physiology, as well as for the design of ephrinA1-based EphA2-targeted antitumor therapeutics. |
| تدمد: | 1476-5594 0950-9232 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3e76e823a52546c3b0f5a840846b30a2 https://doi.org/10.1038/onc.2008.328 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3e76e823a52546c3b0f5a840846b30a2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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