Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance

Autores
Lodillinsky, Catalina; Fuhrmann, Laetitia; Irondelle, Marie; Pylypenko, Olena; Li, Xiao Yan; Bonsang Kitzis, Hélène; Reyal, Fabien; Vacher, Sophie; Calmel, Claire; De Wever, Olivier; Bièche, Ivan; Lacombe, Marie Lise; Eijan, Ana Maria; Houdusse, Anne; Vincent Salomon, Anne; Weiss, Stephen J.; Chavrier, Philippe; Boissan, Mathieu
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Membrane Type 1 Matrix Metalloprotease (MT1-MMP) contributes to the invasive progression of breast cancers by degrading extracellular matrix tissues. Nucleoside diphosphate kinase, NME1/NM23-H1, has been identified as a metastasis suppressor; however, its contribution to local invasion in breast cancer is not known. Here, we report that NME1 is upregulated in ductal carcinoma in situ (DCIS) as compared to normal breast epithelial tissues. NME1 levels drop in microinvasive and invasive components of breast tumor cells relative to synchronous DCIS foci. We find a strong anticorrelation between NME1 and plasma membrane MT1-MMP levels in the invasive components of breast tumors, particularly in aggressive histological grade III and triple-negative breast cancers. Knockout of NME1 accelerates the invasive transition of breast tumors in the intraductal xenograft model. At the mechanistic level, we find that MT1-MMP, NME1 and dynamin-2, a GTPase known to require GTP production by NME1 for its membrane fission activity in the endocytic pathway, interact in clathrin-coated vesicles at the plasma membrane. Loss of NME1 function increases MT1- MMP surface levels by inhibiting endocytic clearance. As a consequence, the ECM degradation and invasive potentials of breast cancer cells are enhanced. This study identifies the down-modulation of NME1 as a potent driver of the in situ-to invasive transition during breast cancer progression.
Fil: Lodillinsky, Catalina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Fuhrmann, Laetitia. Institute Curie; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Irondelle, Marie. Institute Curie; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Pylypenko, Olena. Institute Curie; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Li, Xiao Yan. University of Michigan; Estados Unidos
Fil: Bonsang Kitzis, Hélène. Institute Curie; Francia. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Reyal, Fabien. Institute Curie; Francia. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Vacher, Sophie. Institute Curie; Francia
Fil: Calmel, Claire. Sorbonne University; Francia. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: De Wever, Olivier. University of Ghent; Bélgica
Fil: Bièche, Ivan. Institute Curie; Francia
Fil: Lacombe, Marie Lise. Sorbonne University; Francia. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Eijan, Ana Maria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Houdusse, Anne. Institute Curie; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Vincent Salomon, Anne. Institute Curie; Francia
Fil: Weiss, Stephen J.. University of Michigan; Estados Unidos
Fil: Chavrier, Philippe. Institute Curie; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Boissan, Mathieu. Sorbonne University; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Tenon Hospital; Francia
Materia
BREAST CANCER
MT1-MMP
NME1/NM23-H1
METATATIC GENE SUPRESSOR
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/156834
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/156834
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearanceLodillinsky, CatalinaFuhrmann, LaetitiaIrondelle, MariePylypenko, OlenaLi, Xiao YanBonsang Kitzis, HélèneReyal, FabienVacher, SophieCalmel, ClaireDe Wever, OlivierBièche, IvanLacombe, Marie LiseEijan, Ana MariaHoudusse, AnneVincent Salomon, AnneWeiss, Stephen J.Chavrier, PhilippeBoissan, MathieuBREAST CANCERMT1-MMPNME1/NM23-H1METATATIC GENE SUPRESSORhttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Membrane Type 1 Matrix Metalloprotease (MT1-MMP) contributes to the invasive progression of breast cancers by degrading extracellular matrix tissues. Nucleoside diphosphate kinase, NME1/NM23-H1, has been identified as a metastasis suppressor; however, its contribution to local invasion in breast cancer is not known. Here, we report that NME1 is upregulated in ductal carcinoma in situ (DCIS) as compared to normal breast epithelial tissues. NME1 levels drop in microinvasive and invasive components of breast tumor cells relative to synchronous DCIS foci. We find a strong anticorrelation between NME1 and plasma membrane MT1-MMP levels in the invasive components of breast tumors, particularly in aggressive histological grade III and triple-negative breast cancers. Knockout of NME1 accelerates the invasive transition of breast tumors in the intraductal xenograft model. At the mechanistic level, we find that MT1-MMP, NME1 and dynamin-2, a GTPase known to require GTP production by NME1 for its membrane fission activity in the endocytic pathway, interact in clathrin-coated vesicles at the plasma membrane. Loss of NME1 function increases MT1- MMP surface levels by inhibiting endocytic clearance. As a consequence, the ECM degradation and invasive potentials of breast cancer cells are enhanced. This study identifies the down-modulation of NME1 as a potent driver of the in situ-to invasive transition during breast cancer progression.Fil: Lodillinsky, Catalina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Fuhrmann, Laetitia. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Irondelle, Marie. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Pylypenko, Olena. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Li, Xiao Yan. University of Michigan; Estados UnidosFil: Bonsang Kitzis, Hélène. Institute Curie; Francia. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Reyal, Fabien. Institute Curie; Francia. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Vacher, Sophie. Institute Curie; FranciaFil: Calmel, Claire. Sorbonne University; Francia. Institut National de la Santé et de la Recherche Médicale; FranciaFil: De Wever, Olivier. University of Ghent; BélgicaFil: Bièche, Ivan. Institute Curie; FranciaFil: Lacombe, Marie Lise. Sorbonne University; Francia. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Eijan, Ana Maria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Houdusse, Anne. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Vincent Salomon, Anne. Institute Curie; FranciaFil: Weiss, Stephen J.. University of Michigan; Estados UnidosFil: Chavrier, Philippe. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Boissan, Mathieu. Sorbonne University; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Tenon Hospital; FranciaNature Publishing Group2021-06-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/156834Lodillinsky, Catalina; Fuhrmann, Laetitia; Irondelle, Marie; Pylypenko, Olena; Li, Xiao Yan; et al.; Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance; Nature Publishing Group; Oncogene; 40; 10-6-2021; 1-140950-92321476-5594CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41388-021-01826-1info:eu-repo/semantics/altIdentifier/doi/10.1038/s41388-021-01826-1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:20:18Zoai:ri.conicet.gov.ar:11336/156834instacron: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 10:20:18.846CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance
title Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance
spellingShingle Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance
Lodillinsky, Catalina
BREAST CANCER
MT1-MMP
NME1/NM23-H1
METATATIC GENE SUPRESSOR
title_short Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance
title_full Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance
title_fullStr Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance
title_full_unstemmed Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance
title_sort Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance
dc.creator.none.fl_str_mv Lodillinsky, Catalina
Fuhrmann, Laetitia
Irondelle, Marie
Pylypenko, Olena
Li, Xiao Yan
Bonsang Kitzis, Hélène
Reyal, Fabien
Vacher, Sophie
Calmel, Claire
De Wever, Olivier
Bièche, Ivan
Lacombe, Marie Lise
Eijan, Ana Maria
Houdusse, Anne
Vincent Salomon, Anne
Weiss, Stephen J.
Chavrier, Philippe
Boissan, Mathieu
author Lodillinsky, Catalina
author_facet Lodillinsky, Catalina
Fuhrmann, Laetitia
Irondelle, Marie
Pylypenko, Olena
Li, Xiao Yan
Bonsang Kitzis, Hélène
Reyal, Fabien
Vacher, Sophie
Calmel, Claire
De Wever, Olivier
Bièche, Ivan
Lacombe, Marie Lise
Eijan, Ana Maria
Houdusse, Anne
Vincent Salomon, Anne
Weiss, Stephen J.
Chavrier, Philippe
Boissan, Mathieu
author_role author
author2 Fuhrmann, Laetitia
Irondelle, Marie
Pylypenko, Olena
Li, Xiao Yan
Bonsang Kitzis, Hélène
Reyal, Fabien
Vacher, Sophie
Calmel, Claire
De Wever, Olivier
Bièche, Ivan
Lacombe, Marie Lise
Eijan, Ana Maria
Houdusse, Anne
Vincent Salomon, Anne
Weiss, Stephen J.
Chavrier, Philippe
Boissan, Mathieu
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BREAST CANCER
MT1-MMP
NME1/NM23-H1
METATATIC GENE SUPRESSOR
topic BREAST CANCER
MT1-MMP
NME1/NM23-H1
METATATIC GENE SUPRESSOR
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Membrane Type 1 Matrix Metalloprotease (MT1-MMP) contributes to the invasive progression of breast cancers by degrading extracellular matrix tissues. Nucleoside diphosphate kinase, NME1/NM23-H1, has been identified as a metastasis suppressor; however, its contribution to local invasion in breast cancer is not known. Here, we report that NME1 is upregulated in ductal carcinoma in situ (DCIS) as compared to normal breast epithelial tissues. NME1 levels drop in microinvasive and invasive components of breast tumor cells relative to synchronous DCIS foci. We find a strong anticorrelation between NME1 and plasma membrane MT1-MMP levels in the invasive components of breast tumors, particularly in aggressive histological grade III and triple-negative breast cancers. Knockout of NME1 accelerates the invasive transition of breast tumors in the intraductal xenograft model. At the mechanistic level, we find that MT1-MMP, NME1 and dynamin-2, a GTPase known to require GTP production by NME1 for its membrane fission activity in the endocytic pathway, interact in clathrin-coated vesicles at the plasma membrane. Loss of NME1 function increases MT1- MMP surface levels by inhibiting endocytic clearance. As a consequence, the ECM degradation and invasive potentials of breast cancer cells are enhanced. This study identifies the down-modulation of NME1 as a potent driver of the in situ-to invasive transition during breast cancer progression.
Fil: Lodillinsky, Catalina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Fuhrmann, Laetitia. Institute Curie; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Irondelle, Marie. Institute Curie; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Pylypenko, Olena. Institute Curie; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Li, Xiao Yan. University of Michigan; Estados Unidos
Fil: Bonsang Kitzis, Hélène. Institute Curie; Francia. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Reyal, Fabien. Institute Curie; Francia. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Vacher, Sophie. Institute Curie; Francia
Fil: Calmel, Claire. Sorbonne University; Francia. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: De Wever, Olivier. University of Ghent; Bélgica
Fil: Bièche, Ivan. Institute Curie; Francia
Fil: Lacombe, Marie Lise. Sorbonne University; Francia. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Eijan, Ana Maria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Houdusse, Anne. Institute Curie; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Vincent Salomon, Anne. Institute Curie; Francia
Fil: Weiss, Stephen J.. University of Michigan; Estados Unidos
Fil: Chavrier, Philippe. Institute Curie; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Boissan, Mathieu. Sorbonne University; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Tenon Hospital; Francia
description Membrane Type 1 Matrix Metalloprotease (MT1-MMP) contributes to the invasive progression of breast cancers by degrading extracellular matrix tissues. Nucleoside diphosphate kinase, NME1/NM23-H1, has been identified as a metastasis suppressor; however, its contribution to local invasion in breast cancer is not known. Here, we report that NME1 is upregulated in ductal carcinoma in situ (DCIS) as compared to normal breast epithelial tissues. NME1 levels drop in microinvasive and invasive components of breast tumor cells relative to synchronous DCIS foci. We find a strong anticorrelation between NME1 and plasma membrane MT1-MMP levels in the invasive components of breast tumors, particularly in aggressive histological grade III and triple-negative breast cancers. Knockout of NME1 accelerates the invasive transition of breast tumors in the intraductal xenograft model. At the mechanistic level, we find that MT1-MMP, NME1 and dynamin-2, a GTPase known to require GTP production by NME1 for its membrane fission activity in the endocytic pathway, interact in clathrin-coated vesicles at the plasma membrane. Loss of NME1 function increases MT1- MMP surface levels by inhibiting endocytic clearance. As a consequence, the ECM degradation and invasive potentials of breast cancer cells are enhanced. This study identifies the down-modulation of NME1 as a potent driver of the in situ-to invasive transition during breast cancer progression.
publishDate 2021
dc.date.none.fl_str_mv 2021-06-10
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/11336/156834
Lodillinsky, Catalina; Fuhrmann, Laetitia; Irondelle, Marie; Pylypenko, Olena; Li, Xiao Yan; et al.; Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance; Nature Publishing Group; Oncogene; 40; 10-6-2021; 1-14
0950-9232
1476-5594
CONICET Digital
CONICET
url http://hdl.handle.net/11336/156834
identifier_str_mv Lodillinsky, Catalina; Fuhrmann, Laetitia; Irondelle, Marie; Pylypenko, Olena; Li, Xiao Yan; et al.; Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance; Nature Publishing Group; Oncogene; 40; 10-6-2021; 1-14
0950-9232
1476-5594
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41388-021-01826-1
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41388-021-01826-1
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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
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score 13.070432

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