Actin bundling by dynamin 2 and cortactin is implicated in cell migration by stabilizing filopodia in human non-small cell lung carcinoma cells
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...
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| Veröffentlicht in: | International journal of oncology 2016-09, Vol.49 (3), p.877-886 |
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| creator | Yamada, Hiroshi Takeda, Tetsuya Michiue, Hiroyuki Abe, Tadashi Takei, Kohji |
| description | 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. |
| doi_str_mv | 10.3892/ijo.2016.3592 |
| format | Article |
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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.</description><identifier>ISSN: 1019-6439</identifier><identifier>EISSN: 1791-2423</identifier><identifier>DOI: 10.3892/ijo.2016.3592</identifier><identifier>PMID: 27572123</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Actin ; Actins - metabolism ; Biotechnology ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - metabolism ; Care and treatment ; Cell adhesion & migration ; Cell Line, Tumor ; Cell Movement ; cortactin ; Cortactin - genetics ; Cortactin - metabolism ; Development and progression ; dynamin ; Dynamins - genetics ; Dynamins - metabolism ; filopodia ; Gene Knockdown Techniques ; Genetic aspects ; Guanosine triphosphatase ; Humans ; Immunoglobulins ; Innovations ; Lung cancer ; Lung cancer, Non-small cell ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Metastasis ; migration ; Molecular targeted therapy ; Properties ; Proteins ; Pseudopodia - metabolism</subject><ispartof>International journal of oncology, 2016-09, Vol.49 (3), p.877-886</ispartof><rights>Copyright: © Yamada et al.</rights><rights>COPYRIGHT 2016 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2016</rights><rights>Copyright: © Yamada et al. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c655t-9a142a49580af281990e58700cf814bbe6fc2cb5bb8b453f5f2a30cdabff4dd53</citedby><cites>FETCH-LOGICAL-c655t-9a142a49580af281990e58700cf814bbe6fc2cb5bb8b453f5f2a30cdabff4dd53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,5571,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27572123$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamada, Hiroshi</creatorcontrib><creatorcontrib>Takeda, Tetsuya</creatorcontrib><creatorcontrib>Michiue, Hiroyuki</creatorcontrib><creatorcontrib>Abe, Tadashi</creatorcontrib><creatorcontrib>Takei, Kohji</creatorcontrib><title>Actin bundling by dynamin 2 and cortactin is implicated in cell migration by stabilizing filopodia in human non-small cell lung carcinoma cells</title><title>International journal of oncology</title><addtitle>Int J Oncol</addtitle><description>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.</description><subject>Actin</subject><subject>Actins - metabolism</subject><subject>Biotechnology</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Care and treatment</subject><subject>Cell adhesion & migration</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>cortactin</subject><subject>Cortactin - genetics</subject><subject>Cortactin - metabolism</subject><subject>Development and progression</subject><subject>dynamin</subject><subject>Dynamins - genetics</subject><subject>Dynamins - metabolism</subject><subject>filopodia</subject><subject>Gene Knockdown Techniques</subject><subject>Genetic aspects</subject><subject>Guanosine triphosphatase</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Innovations</subject><subject>Lung cancer</subject><subject>Lung cancer, Non-small cell</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Metastasis</subject><subject>migration</subject><subject>Molecular targeted therapy</subject><subject>Properties</subject><subject>Proteins</subject><subject>Pseudopodia - metabolism</subject><issn>1019-6439</issn><issn>1791-2423</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptkkuLFDEUhQtRnHF06VYKBF1Vm2dVZSM0gy8YcKPrcPPqTpNK2kqV0P4J_7Kp7rGdBski4eY7h5ubU1UvMVrRXpB3fpdWBOF2Rbkgj6pr3AncEEbo43JGWDQto-KqepbzDiHCOcJPqyvS8Y5gQq-r32s9-VirOZrg46ZWh9ocIgylRmqIptZpnODI-Fz7YR-8hsmauhS0DaEe_GaEyae4SPMEygf_a3FyPqR9Mh4WdDsPEOuYYpMHKKqjNMwF0zBqH9MAx1p-Xj1xELJ9cb_fVN8_fvh2-7m5-_rpy-36rtEt51MjADMCTPAegSM9FgJZ3ncIaddjppRtnSZacaV6xTh13BGgSBtQzjFjOL2p3p9897MarNE2TiMEuR_9AONBJvDy8ib6rdykn5IJ1gveFoPX9wZj-jHbPMldmsdYepZYUEIJwYL_ozYQrPTRpWKmB5-1XLOWdsVI0EKt_kOVZezgdYq2zNJeCt48EGwthGmbU5iXf8iXYHMC9ZhyHq07vxAjueRHlvzIJT9yyU_hXz0cy5n-G5gCvD0BeV_S4U3KZ6Y4NUw0iDao7zr6B0Uez4I</recordid><startdate>20160901</startdate><enddate>20160901</enddate><creator>Yamada, Hiroshi</creator><creator>Takeda, Tetsuya</creator><creator>Michiue, Hiroyuki</creator><creator>Abe, Tadashi</creator><creator>Takei, Kohji</creator><general>D.A. 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Abe, Tadashi ; Takei, Kohji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c655t-9a142a49580af281990e58700cf814bbe6fc2cb5bb8b453f5f2a30cdabff4dd53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Actin</topic><topic>Actins - metabolism</topic><topic>Biotechnology</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Care and treatment</topic><topic>Cell adhesion & migration</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>cortactin</topic><topic>Cortactin - genetics</topic><topic>Cortactin - metabolism</topic><topic>Development and progression</topic><topic>dynamin</topic><topic>Dynamins - genetics</topic><topic>Dynamins - metabolism</topic><topic>filopodia</topic><topic>Gene Knockdown Techniques</topic><topic>Genetic aspects</topic><topic>Guanosine triphosphatase</topic><topic>Humans</topic><topic>Immunoglobulins</topic><topic>Innovations</topic><topic>Lung cancer</topic><topic>Lung cancer, Non-small cell</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Metastasis</topic><topic>migration</topic><topic>Molecular targeted therapy</topic><topic>Properties</topic><topic>Proteins</topic><topic>Pseudopodia - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamada, Hiroshi</creatorcontrib><creatorcontrib>Takeda, Tetsuya</creatorcontrib><creatorcontrib>Michiue, Hiroyuki</creatorcontrib><creatorcontrib>Abe, Tadashi</creatorcontrib><creatorcontrib>Takei, Kohji</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamada, Hiroshi</au><au>Takeda, Tetsuya</au><au>Michiue, Hiroyuki</au><au>Abe, Tadashi</au><au>Takei, Kohji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Actin bundling by dynamin 2 and cortactin is implicated in cell migration by stabilizing filopodia in human non-small cell lung carcinoma cells</atitle><jtitle>International journal of oncology</jtitle><addtitle>Int J Oncol</addtitle><date>2016-09-01</date><risdate>2016</risdate><volume>49</volume><issue>3</issue><spage>877</spage><epage>886</epage><pages>877-886</pages><issn>1019-6439</issn><eissn>1791-2423</eissn><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.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>27572123</pmid><doi>10.3892/ijo.2016.3592</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | Spandidos Publications Journals; MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Actin Actins - metabolism Biotechnology Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Care and treatment Cell adhesion & migration Cell Line, Tumor Cell Movement cortactin Cortactin - genetics Cortactin - metabolism Development and progression dynamin Dynamins - genetics Dynamins - metabolism filopodia Gene Knockdown Techniques Genetic aspects Guanosine triphosphatase Humans Immunoglobulins Innovations Lung cancer Lung cancer, Non-small cell Lung Neoplasms - genetics Lung Neoplasms - metabolism Metastasis migration Molecular targeted therapy Properties Proteins Pseudopodia - metabolism |
| title | Actin bundling by dynamin 2 and cortactin is implicated in cell migration by stabilizing filopodia in human non-small cell lung carcinoma cells |
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