Changes in cell morphology guide identification of tubulin as the off-target for protein kinase inhibitors
| Autor: | Ramzi H. Abbassi, Michael Kassiou, Jennifer Man, Monira Hoque, Lenka Munoz, Bryan W. Day, Danielle Froio, Terrance Grant Johns, Marina Pajic, Brett W. Stringer |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Time Factors Cell Survival Antineoplastic Agents macromolecular substances Cell morphology Microtubules Cellular protein 03 medical and health sciences Tubulin Cell Line Tumor Neoplasms medicine Humans Kinome Protein kinase A Cell Shape Protein Kinase Inhibitors Pharmacology biology Chemistry Kinase Cell Cycle medicine.disease Tubulin Modulators Cell biology 030104 developmental biology biology.protein Neoplastic Stem Cells A kinase Glioblastoma |
| Zdroj: | Pharmacological research. 134 |
| ISSN: | 1096-1186 |
| Popis: | In the field of kinase inhibitors for applications in cancer research, tubulin is emerging as a targeted cellular protein that can significantly contribute to their activities. However, investigation of kinase inhibitors beyond the kinome is an area often neglected. Herein, we describe the results of pharmacological studies using drugs targeting kinases, tubulin or both. A key finding is that if cells are treated with a kinase inhibitor unintentionally targeting tubulin, their characteristic shape will diminish within a short timeframe. These changes in cell morphology are not seen when cells are treated with bona fide kinase inhibitors that do not directly target tubulin. Thus, early changes in cell morphology upon treatments are a strong indication that the inhibitor is directly targeting tubulin. Recognizing tubulin as a target of kinase inhibitors will build confidence in the future mechanistic studies using kinase inhibitors. |
| Databáze: | OpenAIRE |
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