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
- ,
- ,
- ,
- ,
- 巻
- 49
- 号
- 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