Dynasore, a dynamin inhibitor, suppresses lamellipodia formation and cancer cell invasion by destabilizing actin filaments
| Autor: | Yuki Masuoka, Shun Ai Li, Tadashi Abe, Hiromi Kumon, Mihoko Isoda, Hiroshi Yamada, Akira Asai, Yasutomo Nasu, Kohji Takei, Masami Watanabe |
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| Rok vydání: | 2009 |
| Předmět: |
Lung Neoplasms
Cell Biophysics Motility Antineoplastic Agents macromolecular substances Biochemistry Dynamin II Cell Line Tumor medicine Humans Neoplasm Invasiveness Pseudopodia Molecular Biology Actin Dynamin biology Hydrazones Cell Biology Actin cytoskeleton Cell biology Actin Cytoskeleton medicine.anatomical_structure biology.protein Lamellipodium Cortactin |
| Zdroj: | Biochemical and Biophysical Research Communications. 390:1142-1148 |
| ISSN: | 0006-291X |
| Popis: | Dynamic remodeling of actin filaments are bases for a variety of cellular events including cell motility and cancer invasion, and the regulation of actin dynamics implies dynamin, well characterized endocytotic protein. Here we report that dynasore, a inhibitor of dynamin GTPase, potently destabilizes F-actin in vitro, and it severely inhibits the formation of pseudopodia and cancer cell invasion, both of which are supported by active F-actin formation. Dynasore rapidly disrupted F-actin formed in brain cytosol in vitro, and the dynasore's effect on F-actin was indirect. Dynasore significantly suppressed serum-induced lamellipodia formation in U2OS cell. Dynasore also destabilized F-actin in resting cells, which caused the retraction of the plasma membrane. A certain amount of dynamin 2 in U2OS cells localized along F-actin, and co-localized with cortactin, a physiological binding partner of dynamin and F-actin. However, these associations of dynamin were partially disrupted by dynasore treatment. Furthermore, invasion activity of H1080 cell, a lung cancer cell line, was suppressed by approximately 40% with dynasore treatment. These results strongly suggest that dynasore potently destabilizes F-actin, and the effect implies dynamin. Dynasore or its derivative would be suitable candidates as potent anti-cancer drugs. |
| Databáze: | OpenAIRE |
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