Dynasore, a dynamin inhibitor, suppresses lamellipodia formation and cancer cell invasion by destabilizing actin filaments

Hiroshi Yamada, Tadashi Abe, Shun Ai Li, Yuki Masuoka, Mihoko Isoda, Masami Watanabe, Yasutomo Nasu, Hiromi Kumon, Akira Asai, Kohji Takei

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1142-1148
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume390
Issue number4
DOIs
Publication statusPublished - Dec 25 2009

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Keywords

  • Actin cytoskeleton
  • Cortactin
  • Dynamin
  • Dynasore
  • Invasion
  • Lamellipodia

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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