Rho/ROCK pathway inhibition by CDK inhibitor p27kip1 participates in the onset of macrophage 3D-mesenchymal migration

Macrophage tissue infiltration can promote tumour development. Depending on the extracellular matrix architecture, macrophages can adopt two migration modes: amoeboid (AM), common to all leukocytes; and mesenchymal (MM), restricted to macrophages and certain tumour cells. Here, we investigated the i...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of cell science 2014-01, Vol.127 (18), p.4009-4023
Hauptverfasser: Gui, Philippe, Labrousse, Arnaud, Van Goethem, Emeline, Besson, Arnaud, Maridonneau-Parini, Isabelle, Le Cabec, Véronique
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 4023
container_issue 18
container_start_page 4009
container_title Journal of cell science
container_volume 127
creator Gui, Philippe
Labrousse, Arnaud
Van Goethem, Emeline
Besson, Arnaud
Maridonneau-Parini, Isabelle
Le Cabec, Véronique
description Macrophage tissue infiltration can promote tumour development. Depending on the extracellular matrix architecture, macrophages can adopt two migration modes: amoeboid (AM), common to all leukocytes; and mesenchymal (MM), restricted to macrophages and certain tumour cells. Here, we investigated the initiating mechanisms involved in macrophage MM. We show that a single macrophage is able to use both migration modes. Macrophage MM is correlated with a decreased Rho/Rho-associated protein kinase (ROCK) activity and potentiated by ROCK inhibition, suggesting that AM inhibition could participate in MM initiating mechanisms. We identify the cyclin-dependent kinase (CDK) inhibitor p27kip1 as a new effector of macrophage 3D-migration. Using p27kip1 siRNA and p27kip1 mutant mice, we show that p27kip1 promotes MM and hinders AM upstream of the Rho/ROCK pathway, a process associated with a relocation of the protein from the nucleus to the cytoplasm. Finally, we observe that cytoplasmic p27kip1 is required for in vivo macrophage tissue infiltration in induced tumours in mice. This study provides the first evidence that silencing of AM through inhibition of the Rho/ROCK pathway by p27kip1 participates in the onset of macrophage MM.
doi_str_mv 10.1242/jcs.150987
format Article
fullrecord <record><control><sourceid>hal_cross</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_02356009v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>oai_HAL_hal_02356009v1</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2127-68ba354d8f456bd6b40dab225775e39e1ca1c551068ce58f331afb77da85a9933</originalsourceid><addsrcrecordid>eNo9kF1LwzAYhYMoOKc3_oLcKnTLR9M0l6NTJxsMhl6XN2m6ZK4fNFXpv7dj6tUL533O4XAQuqdkRlnM5gcTZlQQlcoLNKGxlJGiXF6iCSGMRkpwfo1uQjgQQiRTcoI-d66Z77bZGrfQu28YsK-d1773TY31gLPl-k9pOtwy-eFbOrJd740fLTaMb9w7i5s62B43Ja7AdE3rYG8xX0aVDbY2bqjgiCu_7-CUfIuuSjgGe_d7p-j9-ektW0Wb7ctrtthEhlEmoyTVwEVcpGUsEl0kOiYFaMaElMJyZakBaoSgJEmNFWnJOYVSS1lAKkApzqfo4Zzr4Ji3na-gG_IGfL5abPKTRhgXCSHqi47s45kd24fQ2fLfQEl-Gjcfx83P4_Ifcqhsow</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Rho/ROCK pathway inhibition by CDK inhibitor p27kip1 participates in the onset of macrophage 3D-mesenchymal migration</title><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><source>Company of Biologists</source><creator>Gui, Philippe ; Labrousse, Arnaud ; Van Goethem, Emeline ; Besson, Arnaud ; Maridonneau-Parini, Isabelle ; Le Cabec, Véronique</creator><creatorcontrib>Gui, Philippe ; Labrousse, Arnaud ; Van Goethem, Emeline ; Besson, Arnaud ; Maridonneau-Parini, Isabelle ; Le Cabec, Véronique</creatorcontrib><description>Macrophage tissue infiltration can promote tumour development. Depending on the extracellular matrix architecture, macrophages can adopt two migration modes: amoeboid (AM), common to all leukocytes; and mesenchymal (MM), restricted to macrophages and certain tumour cells. Here, we investigated the initiating mechanisms involved in macrophage MM. We show that a single macrophage is able to use both migration modes. Macrophage MM is correlated with a decreased Rho/Rho-associated protein kinase (ROCK) activity and potentiated by ROCK inhibition, suggesting that AM inhibition could participate in MM initiating mechanisms. We identify the cyclin-dependent kinase (CDK) inhibitor p27kip1 as a new effector of macrophage 3D-migration. Using p27kip1 siRNA and p27kip1 mutant mice, we show that p27kip1 promotes MM and hinders AM upstream of the Rho/ROCK pathway, a process associated with a relocation of the protein from the nucleus to the cytoplasm. Finally, we observe that cytoplasmic p27kip1 is required for in vivo macrophage tissue infiltration in induced tumours in mice. This study provides the first evidence that silencing of AM through inhibition of the Rho/ROCK pathway by p27kip1 participates in the onset of macrophage MM.</description><identifier>ISSN: 0021-9533</identifier><identifier>EISSN: 1477-9137</identifier><identifier>DOI: 10.1242/jcs.150987</identifier><language>eng</language><publisher>Company of Biologists</publisher><subject>Cellular Biology ; Life Sciences</subject><ispartof>Journal of cell science, 2014-01, Vol.127 (18), p.4009-4023</ispartof><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2127-68ba354d8f456bd6b40dab225775e39e1ca1c551068ce58f331afb77da85a9933</citedby><cites>FETCH-LOGICAL-c2127-68ba354d8f456bd6b40dab225775e39e1ca1c551068ce58f331afb77da85a9933</cites><orcidid>0000-0001-8822-3548 ; 0000-0003-0189-0976</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3676,27922,27923</link.rule.ids><backlink>$$Uhttps://hal.science/hal-02356009$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Gui, Philippe</creatorcontrib><creatorcontrib>Labrousse, Arnaud</creatorcontrib><creatorcontrib>Van Goethem, Emeline</creatorcontrib><creatorcontrib>Besson, Arnaud</creatorcontrib><creatorcontrib>Maridonneau-Parini, Isabelle</creatorcontrib><creatorcontrib>Le Cabec, Véronique</creatorcontrib><title>Rho/ROCK pathway inhibition by CDK inhibitor p27kip1 participates in the onset of macrophage 3D-mesenchymal migration</title><title>Journal of cell science</title><description>Macrophage tissue infiltration can promote tumour development. Depending on the extracellular matrix architecture, macrophages can adopt two migration modes: amoeboid (AM), common to all leukocytes; and mesenchymal (MM), restricted to macrophages and certain tumour cells. Here, we investigated the initiating mechanisms involved in macrophage MM. We show that a single macrophage is able to use both migration modes. Macrophage MM is correlated with a decreased Rho/Rho-associated protein kinase (ROCK) activity and potentiated by ROCK inhibition, suggesting that AM inhibition could participate in MM initiating mechanisms. We identify the cyclin-dependent kinase (CDK) inhibitor p27kip1 as a new effector of macrophage 3D-migration. Using p27kip1 siRNA and p27kip1 mutant mice, we show that p27kip1 promotes MM and hinders AM upstream of the Rho/ROCK pathway, a process associated with a relocation of the protein from the nucleus to the cytoplasm. Finally, we observe that cytoplasmic p27kip1 is required for in vivo macrophage tissue infiltration in induced tumours in mice. This study provides the first evidence that silencing of AM through inhibition of the Rho/ROCK pathway by p27kip1 participates in the onset of macrophage MM.</description><subject>Cellular Biology</subject><subject>Life Sciences</subject><issn>0021-9533</issn><issn>1477-9137</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNo9kF1LwzAYhYMoOKc3_oLcKnTLR9M0l6NTJxsMhl6XN2m6ZK4fNFXpv7dj6tUL533O4XAQuqdkRlnM5gcTZlQQlcoLNKGxlJGiXF6iCSGMRkpwfo1uQjgQQiRTcoI-d66Z77bZGrfQu28YsK-d1773TY31gLPl-k9pOtwy-eFbOrJd740fLTaMb9w7i5s62B43Ja7AdE3rYG8xX0aVDbY2bqjgiCu_7-CUfIuuSjgGe_d7p-j9-ektW0Wb7ctrtthEhlEmoyTVwEVcpGUsEl0kOiYFaMaElMJyZakBaoSgJEmNFWnJOYVSS1lAKkApzqfo4Zzr4Ji3na-gG_IGfL5abPKTRhgXCSHqi47s45kd24fQ2fLfQEl-Gjcfx83P4_Ifcqhsow</recordid><startdate>20140101</startdate><enddate>20140101</enddate><creator>Gui, Philippe</creator><creator>Labrousse, Arnaud</creator><creator>Van Goethem, Emeline</creator><creator>Besson, Arnaud</creator><creator>Maridonneau-Parini, Isabelle</creator><creator>Le Cabec, Véronique</creator><general>Company of Biologists</general><scope>AAYXX</scope><scope>CITATION</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0001-8822-3548</orcidid><orcidid>https://orcid.org/0000-0003-0189-0976</orcidid></search><sort><creationdate>20140101</creationdate><title>Rho/ROCK pathway inhibition by CDK inhibitor p27kip1 participates in the onset of macrophage 3D-mesenchymal migration</title><author>Gui, Philippe ; Labrousse, Arnaud ; Van Goethem, Emeline ; Besson, Arnaud ; Maridonneau-Parini, Isabelle ; Le Cabec, Véronique</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2127-68ba354d8f456bd6b40dab225775e39e1ca1c551068ce58f331afb77da85a9933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Cellular Biology</topic><topic>Life Sciences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gui, Philippe</creatorcontrib><creatorcontrib>Labrousse, Arnaud</creatorcontrib><creatorcontrib>Van Goethem, Emeline</creatorcontrib><creatorcontrib>Besson, Arnaud</creatorcontrib><creatorcontrib>Maridonneau-Parini, Isabelle</creatorcontrib><creatorcontrib>Le Cabec, Véronique</creatorcontrib><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Journal of cell science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gui, Philippe</au><au>Labrousse, Arnaud</au><au>Van Goethem, Emeline</au><au>Besson, Arnaud</au><au>Maridonneau-Parini, Isabelle</au><au>Le Cabec, Véronique</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rho/ROCK pathway inhibition by CDK inhibitor p27kip1 participates in the onset of macrophage 3D-mesenchymal migration</atitle><jtitle>Journal of cell science</jtitle><date>2014-01-01</date><risdate>2014</risdate><volume>127</volume><issue>18</issue><spage>4009</spage><epage>4023</epage><pages>4009-4023</pages><issn>0021-9533</issn><eissn>1477-9137</eissn><abstract>Macrophage tissue infiltration can promote tumour development. Depending on the extracellular matrix architecture, macrophages can adopt two migration modes: amoeboid (AM), common to all leukocytes; and mesenchymal (MM), restricted to macrophages and certain tumour cells. Here, we investigated the initiating mechanisms involved in macrophage MM. We show that a single macrophage is able to use both migration modes. Macrophage MM is correlated with a decreased Rho/Rho-associated protein kinase (ROCK) activity and potentiated by ROCK inhibition, suggesting that AM inhibition could participate in MM initiating mechanisms. We identify the cyclin-dependent kinase (CDK) inhibitor p27kip1 as a new effector of macrophage 3D-migration. Using p27kip1 siRNA and p27kip1 mutant mice, we show that p27kip1 promotes MM and hinders AM upstream of the Rho/ROCK pathway, a process associated with a relocation of the protein from the nucleus to the cytoplasm. Finally, we observe that cytoplasmic p27kip1 is required for in vivo macrophage tissue infiltration in induced tumours in mice. This study provides the first evidence that silencing of AM through inhibition of the Rho/ROCK pathway by p27kip1 participates in the onset of macrophage MM.</abstract><pub>Company of Biologists</pub><doi>10.1242/jcs.150987</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-8822-3548</orcidid><orcidid>https://orcid.org/0000-0003-0189-0976</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0021-9533
ispartof Journal of cell science, 2014-01, Vol.127 (18), p.4009-4023
issn 0021-9533
1477-9137
language eng
recordid cdi_hal_primary_oai_HAL_hal_02356009v1
source EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Company of Biologists
subjects Cellular Biology
Life Sciences
title Rho/ROCK pathway inhibition by CDK inhibitor p27kip1 participates in the onset of macrophage 3D-mesenchymal migration
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T18%3A27%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-hal_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Rho/ROCK%20pathway%20inhibition%20by%20CDK%20inhibitor%20p27kip1%20participates%20in%20the%20onset%20of%20macrophage%203D-mesenchymal%20migration&rft.jtitle=Journal%20of%20cell%20science&rft.au=Gui,%20Philippe&rft.date=2014-01-01&rft.volume=127&rft.issue=18&rft.spage=4009&rft.epage=4023&rft.pages=4009-4023&rft.issn=0021-9533&rft.eissn=1477-9137&rft_id=info:doi/10.1242/jcs.150987&rft_dat=%3Chal_cross%3Eoai_HAL_hal_02356009v1%3C/hal_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true