MISC

国際誌
2016年9月

Actin bundling by dynamin 2 and cortactin is implicated in cell migration by stabilizing filopodia in human non-small cell lung carcinoma cells

INTERNATIONAL JOURNAL OF ONCOLOGY
  • Hiroshi Yamada
  • ,
  • Tetsuya Takeda
  • ,
  • Hiroyuki Michiue
  • ,
  • Tadashi Abe
  • ,
  • Kohji Takei

49
3
開始ページ
877
終了ページ
886
記述言語
英語
掲載種別
DOI
10.3892/ijo.2016.3592
出版者・発行元
SPANDIDOS PUBL LTD

The endocytic protein dynamin participates in the formation of actin-based membrane protrusions such as podosomes, pseudopodia, and invadopodia, which facilitate cancer cell migration, invasion, and metastasis. However, the role of dynamin in the formation of actin-based membrane protrusions at the leading edge of cancer cells is unclear. In this study, we demonstrate that the ubiquitously expressed dynamin 2 isoform facilitates cell migration by stabilizing F-actin bundles in filopodia of the lung cancer cell line H1299. Pharmacological inhibition of dynamin 2 decreased cell migration and filopodial formation. Furthermore, dynamin 2 and cortactin mostly colocalized along F-actin bundles in filopodia of serum-stimulated H1299 cells by immunofluorescent and immunoelectron microscopy. Knockdown of dynamin 2 or cortactin inhibited the formation of filopodia in serum-stimulated H1299 cells, concomitant with a loss of F-actin bundles. Expression of wild-type cortactin rescued the punctate-like localization of dynamin 2 and filopodial formation. The incubation of dynamin 2 and cortactin with F-actin induced the formation of long and thick actin bundles, with these proteins colocalizing at F-actin bundles. A depolymerization assay revealed that dynamin 2 and cortactin increased the stability of F-actin bundles. These results indicate that dynamin 2 and cortactin participate in cell migration by stabilizing F-actin bundles in filopodia. Taken together, these findings suggest that dynamin might be a possible molecular target for anticancer therapy.


リンク情報
DOI
https://doi.org/10.3892/ijo.2016.3592
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27572123
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948956
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000382447300003&DestApp=WOS_CPL
ID情報
  • DOI : 10.3892/ijo.2016.3592
  • ISSN : 1019-6439
  • eISSN : 1791-2423
  • PubMed ID : 27572123
  • PubMed Central 記事ID : PMC4948956
  • Web of Science ID : WOS:000382447300003

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