ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion

Autores
Marchesin, Valentina; Castro Castro, Antonio; Lodillinsky, Catalina; Castagnino, Alessia; Cyrta, Joanna; Bonsang Kitzis, Hélène; Fuhrmann, Laetitia; Irondelle, Marie; Infante, Elvira; Montagnac, Guillaume; Reyal, Fabien; Vincent Salomon, Anne; Chavrier, Philippe
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Invasion of cancer cells into collagen-rich extracellular matrix requires membrane-tethered membrane type 1-matrix metalloproteinase (MT1-MMP) as the key protease for collagen breakdown. Understanding how MT1-MMP is delivered to the surface of tumor cells is essential for cancer cell biology. In this study, we identify ARF6 together with c-Jun NH2-terminal kinase-interacting protein 3 and 4 (JIP3 and JIP4) effectors as critical regulators of this process. Silencing ARF6 or JIP3/JIP4 in breast tumor cells results in MT1-MMP endosome mispositioning and reduces MT1-MMP exocytosis and tumor cell invasion. JIPs are recruited by Wiskott-Aldrich syndrome protein and scar homologue (WASH) on MT1-MMP endosomes on which they recruit dynein-dynactin and kinesin-1. The interaction of plasma membrane ARF6 with endosomal JIPs coordinates dynactin-dynein and kinesin-1 activity in a tug-of-war mechanism, leading to MT1-MMP endosome tubulation and exocytosis. In addition, we find that ARF6, MT1-MMP, and kinesin-1 are up-regulated in high-grade triple-negative breast cancers. These data identify a critical ARF6-JIP-MT1-MMP-dynein-dynactin-kinesin-1 axis promoting an invasive phenotype of breast cancer cells.
Fil: Marchesin, Valentina. Université de recherche Paris Sciences et Lettres; Francia. Universite Pierre et Marie Curie; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Castro Castro, Antonio. Université de recherche Paris Sciences et Lettres; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Lodillinsky, Catalina. Université de recherche Paris Sciences et Lettres; Francia. Centre National de la Recherche Scientifique; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Castagnino, Alessia. Centre National de la Recherche Scientifique; Francia. Université de recherche Paris Sciences et Lettres; Francia
Fil: Cyrta, Joanna. Centre National de la Recherche Scientifique; Francia. Université de recherche Paris Sciences et Lettres; Francia
Fil: Bonsang Kitzis, Hélène. Institut Curie; Francia
Fil: Fuhrmann, Laetitia. Institut Curie; Francia
Fil: Irondelle, Marie. Centre National de la Recherche Scientifique; Francia. Université de recherche Paris Sciences et Lettres; Francia
Fil: Infante, Elvira. Centre National de la Recherche Scientifique; Francia. Université de recherche Paris Sciences et Lettres; Francia
Fil: Montagnac, Guillaume. Centre National de la Recherche Scientifique; Francia. Université de recherche Paris Sciences et Lettres; Francia
Fil: Reyal, Fabien. Institut Curie; Francia
Fil: Vincent Salomon, Anne. Institut Curie; Francia
Fil: Chavrier, Philippe. Université de recherche Paris Sciences et Lettres; Francia. Centre National de la Recherche Scientifique; Francia
Materia
Mt1-Mmp
Arf6
Breast Cancer
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/38856
Acceder
id CONICETDig_68389cb5afae246767e0c93dfaaadf85
oai_identifier_str oai:ri.conicet.gov.ar:11336/38856
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasionMarchesin, ValentinaCastro Castro, AntonioLodillinsky, CatalinaCastagnino, AlessiaCyrta, JoannaBonsang Kitzis, HélèneFuhrmann, LaetitiaIrondelle, MarieInfante, ElviraMontagnac, GuillaumeReyal, FabienVincent Salomon, AnneChavrier, PhilippeMt1-MmpArf6Breast Cancerhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Invasion of cancer cells into collagen-rich extracellular matrix requires membrane-tethered membrane type 1-matrix metalloproteinase (MT1-MMP) as the key protease for collagen breakdown. Understanding how MT1-MMP is delivered to the surface of tumor cells is essential for cancer cell biology. In this study, we identify ARF6 together with c-Jun NH2-terminal kinase-interacting protein 3 and 4 (JIP3 and JIP4) effectors as critical regulators of this process. Silencing ARF6 or JIP3/JIP4 in breast tumor cells results in MT1-MMP endosome mispositioning and reduces MT1-MMP exocytosis and tumor cell invasion. JIPs are recruited by Wiskott-Aldrich syndrome protein and scar homologue (WASH) on MT1-MMP endosomes on which they recruit dynein-dynactin and kinesin-1. The interaction of plasma membrane ARF6 with endosomal JIPs coordinates dynactin-dynein and kinesin-1 activity in a tug-of-war mechanism, leading to MT1-MMP endosome tubulation and exocytosis. In addition, we find that ARF6, MT1-MMP, and kinesin-1 are up-regulated in high-grade triple-negative breast cancers. These data identify a critical ARF6-JIP-MT1-MMP-dynein-dynactin-kinesin-1 axis promoting an invasive phenotype of breast cancer cells.Fil: Marchesin, Valentina. Université de recherche Paris Sciences et Lettres; Francia. Universite Pierre et Marie Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Castro Castro, Antonio. Université de recherche Paris Sciences et Lettres; Francia. Centre National de la Recherche Scientifique; FranciaFil: Lodillinsky, Catalina. Université de recherche Paris Sciences et Lettres; Francia. Centre National de la Recherche Scientifique; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castagnino, Alessia. Centre National de la Recherche Scientifique; Francia. Université de recherche Paris Sciences et Lettres; FranciaFil: Cyrta, Joanna. Centre National de la Recherche Scientifique; Francia. Université de recherche Paris Sciences et Lettres; FranciaFil: Bonsang Kitzis, Hélène. Institut Curie; FranciaFil: Fuhrmann, Laetitia. Institut Curie; FranciaFil: Irondelle, Marie. Centre National de la Recherche Scientifique; Francia. Université de recherche Paris Sciences et Lettres; FranciaFil: Infante, Elvira. Centre National de la Recherche Scientifique; Francia. Université de recherche Paris Sciences et Lettres; FranciaFil: Montagnac, Guillaume. Centre National de la Recherche Scientifique; Francia. Université de recherche Paris Sciences et Lettres; FranciaFil: Reyal, Fabien. Institut Curie; FranciaFil: Vincent Salomon, Anne. Institut Curie; FranciaFil: Chavrier, Philippe. Université de recherche Paris Sciences et Lettres; Francia. Centre National de la Recherche Scientifique; FranciaRockefeller University Press2015-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/38856Marchesin, Valentina; Castro Castro, Antonio; Lodillinsky, Catalina; Castagnino, Alessia; Cyrta, Joanna; et al.; ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion; Rockefeller University Press; Journal of Cell Biology; 211; 2; 10-2015; 339-3580021-95251540-8140CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1083/jcb.201506002info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621834/info:eu-repo/semantics/altIdentifier/url/http://jcb.rupress.org/content/211/2/339.longinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:26:59Zoai:ri.conicet.gov.ar:11336/38856instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:26:59.319CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion
title ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion
spellingShingle ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion
Marchesin, Valentina
Mt1-Mmp
Arf6
Breast Cancer
title_short ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion
title_full ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion
title_fullStr ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion
title_full_unstemmed ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion
title_sort ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion
dc.creator.none.fl_str_mv Marchesin, Valentina
Castro Castro, Antonio
Lodillinsky, Catalina
Castagnino, Alessia
Cyrta, Joanna
Bonsang Kitzis, Hélène
Fuhrmann, Laetitia
Irondelle, Marie
Infante, Elvira
Montagnac, Guillaume
Reyal, Fabien
Vincent Salomon, Anne
Chavrier, Philippe
author Marchesin, Valentina
author_facet Marchesin, Valentina
Castro Castro, Antonio
Lodillinsky, Catalina
Castagnino, Alessia
Cyrta, Joanna
Bonsang Kitzis, Hélène
Fuhrmann, Laetitia
Irondelle, Marie
Infante, Elvira
Montagnac, Guillaume
Reyal, Fabien
Vincent Salomon, Anne
Chavrier, Philippe
author_role author
author2 Castro Castro, Antonio
Lodillinsky, Catalina
Castagnino, Alessia
Cyrta, Joanna
Bonsang Kitzis, Hélène
Fuhrmann, Laetitia
Irondelle, Marie
Infante, Elvira
Montagnac, Guillaume
Reyal, Fabien
Vincent Salomon, Anne
Chavrier, Philippe
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mt1-Mmp
Arf6
Breast Cancer
topic Mt1-Mmp
Arf6
Breast Cancer
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Invasion of cancer cells into collagen-rich extracellular matrix requires membrane-tethered membrane type 1-matrix metalloproteinase (MT1-MMP) as the key protease for collagen breakdown. Understanding how MT1-MMP is delivered to the surface of tumor cells is essential for cancer cell biology. In this study, we identify ARF6 together with c-Jun NH2-terminal kinase-interacting protein 3 and 4 (JIP3 and JIP4) effectors as critical regulators of this process. Silencing ARF6 or JIP3/JIP4 in breast tumor cells results in MT1-MMP endosome mispositioning and reduces MT1-MMP exocytosis and tumor cell invasion. JIPs are recruited by Wiskott-Aldrich syndrome protein and scar homologue (WASH) on MT1-MMP endosomes on which they recruit dynein-dynactin and kinesin-1. The interaction of plasma membrane ARF6 with endosomal JIPs coordinates dynactin-dynein and kinesin-1 activity in a tug-of-war mechanism, leading to MT1-MMP endosome tubulation and exocytosis. In addition, we find that ARF6, MT1-MMP, and kinesin-1 are up-regulated in high-grade triple-negative breast cancers. These data identify a critical ARF6-JIP-MT1-MMP-dynein-dynactin-kinesin-1 axis promoting an invasive phenotype of breast cancer cells.
Fil: Marchesin, Valentina. Université de recherche Paris Sciences et Lettres; Francia. Universite Pierre et Marie Curie; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Castro Castro, Antonio. Université de recherche Paris Sciences et Lettres; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Lodillinsky, Catalina. Université de recherche Paris Sciences et Lettres; Francia. Centre National de la Recherche Scientifique; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Castagnino, Alessia. Centre National de la Recherche Scientifique; Francia. Université de recherche Paris Sciences et Lettres; Francia
Fil: Cyrta, Joanna. Centre National de la Recherche Scientifique; Francia. Université de recherche Paris Sciences et Lettres; Francia
Fil: Bonsang Kitzis, Hélène. Institut Curie; Francia
Fil: Fuhrmann, Laetitia. Institut Curie; Francia
Fil: Irondelle, Marie. Centre National de la Recherche Scientifique; Francia. Université de recherche Paris Sciences et Lettres; Francia
Fil: Infante, Elvira. Centre National de la Recherche Scientifique; Francia. Université de recherche Paris Sciences et Lettres; Francia
Fil: Montagnac, Guillaume. Centre National de la Recherche Scientifique; Francia. Université de recherche Paris Sciences et Lettres; Francia
Fil: Reyal, Fabien. Institut Curie; Francia
Fil: Vincent Salomon, Anne. Institut Curie; Francia
Fil: Chavrier, Philippe. Université de recherche Paris Sciences et Lettres; Francia. Centre National de la Recherche Scientifique; Francia
description Invasion of cancer cells into collagen-rich extracellular matrix requires membrane-tethered membrane type 1-matrix metalloproteinase (MT1-MMP) as the key protease for collagen breakdown. Understanding how MT1-MMP is delivered to the surface of tumor cells is essential for cancer cell biology. In this study, we identify ARF6 together with c-Jun NH2-terminal kinase-interacting protein 3 and 4 (JIP3 and JIP4) effectors as critical regulators of this process. Silencing ARF6 or JIP3/JIP4 in breast tumor cells results in MT1-MMP endosome mispositioning and reduces MT1-MMP exocytosis and tumor cell invasion. JIPs are recruited by Wiskott-Aldrich syndrome protein and scar homologue (WASH) on MT1-MMP endosomes on which they recruit dynein-dynactin and kinesin-1. The interaction of plasma membrane ARF6 with endosomal JIPs coordinates dynactin-dynein and kinesin-1 activity in a tug-of-war mechanism, leading to MT1-MMP endosome tubulation and exocytosis. In addition, we find that ARF6, MT1-MMP, and kinesin-1 are up-regulated in high-grade triple-negative breast cancers. These data identify a critical ARF6-JIP-MT1-MMP-dynein-dynactin-kinesin-1 axis promoting an invasive phenotype of breast cancer cells.
publishDate 2015
dc.date.none.fl_str_mv 2015-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/38856
Marchesin, Valentina; Castro Castro, Antonio; Lodillinsky, Catalina; Castagnino, Alessia; Cyrta, Joanna; et al.; ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion; Rockefeller University Press; Journal of Cell Biology; 211; 2; 10-2015; 339-358
0021-9525
1540-8140
CONICET Digital
CONICET
url http://hdl.handle.net/11336/38856
identifier_str_mv Marchesin, Valentina; Castro Castro, Antonio; Lodillinsky, Catalina; Castagnino, Alessia; Cyrta, Joanna; et al.; ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion; Rockefeller University Press; Journal of Cell Biology; 211; 2; 10-2015; 339-358
0021-9525
1540-8140
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1083/jcb.201506002
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621834/
info:eu-repo/semantics/altIdentifier/url/http://jcb.rupress.org/content/211/2/339.long
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Rockefeller University Press
publisher.none.fl_str_mv Rockefeller University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844614271405654016
score 13.070432

Publicaciones similares