Open Access

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

  • Authors:
    • Hiroshi Yamada
    • Tetsuya Takeda
    • Hiroyuki Michiue
    • Tadashi Abe
    • Kohji Takei
  • View Affiliations

  • Published online on: June 30, 2016     https://doi.org/10.3892/ijo.2016.3592
  • Pages: 877-886
  • Copyright: © Yamada et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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September 2016
Volume 49 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Yamada, H., Takeda, T., Michiue, H., Abe, T., & Takei, K. (2016). 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, 49, 877-886. https://doi.org/10.3892/ijo.2016.3592
MLA
Yamada, H., Takeda, T., Michiue, H., Abe, T., Takei, K."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 49.3 (2016): 877-886.
Chicago
Yamada, H., Takeda, T., Michiue, H., Abe, T., Takei, K."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 49, no. 3 (2016): 877-886. https://doi.org/10.3892/ijo.2016.3592