期刊
INTERNATIONAL JOURNAL OF ONCOLOGY
卷 49, 期 3, 页码 877-886出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2016.3592
关键词
actin; cortactin; dynamin; filopodia; migration
类别
资金
- Ministry of Education, Science, Sports, and Culture of Japan [26670201, 15K1533007]
- Astellas Foundation for Research on Metabolic Disorders
- Japan Foundation for Applied Enzymology
- Grants-in-Aid for Scientific Research [26670201, 15K15330, 15K10333, 16K10756] Funding Source: KAKEN
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.
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