Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling

Autores
Levental, Kandice R.; Yu, Hongmei; Kass, Laura; Lakins, Johnathon N.; Egeblad, Mikala; Erler, Janine T.; Fong, Sheri F.T.; Csiszar, Katalin; Giaccia, Amato; Weninger, Wolfgang; Yamauchi, Mitsuo; Gasser, David L.; Weaver, Valerie M.
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Tumors are characterized by extracellular matrix (ECM) remodeling and stiffening. The importance of ECM remodeling to cancer is appreciated; the relevance of stiffening is less clear. We found that breast tumorigenesis is accompanied by collagen crosslinking, ECM stiffening, and increased focal adhesions. Induction of collagen crosslinking stiffened the ECM, promoted focal adhesions, enhanced PI3 kinase (PI3K) activity, and induced the invasion of an oncogene-initiated epithelium. Inhibition of integrin signaling repressed the invasion of a premalignant epithelium into a stiffened, crosslinked ECM and forced integrin clustering promoted focal adhesions, enhanced PI3K signaling, and induced the invasion of a premalignant epithelium. Consistently, reduction of lysyl oxidase-mediated collagen crosslinking prevented MMTV-Neu-induced fibrosis, decreased focal adhesions and PI3K activity, impeded malignancy, and lowered tumor incidence. These data show how collagen crosslinking can modulate tissue fibrosis and stiffness to force focal adhesions, growth factor signaling and breast malignancy.
Fil: Levental, Kandice R.. State University of Pennsylvania; Estados Unidos
Fil: Yu, Hongmei. University of California; Estados Unidos
Fil: Kass, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina
Fil: Lakins, Johnathon N.. University of California; Estados Unidos
Fil: Egeblad, Mikala. University of California; Estados Unidos
Fil: Erler, Janine T.. Stanford University School of Medicine; Estados Unidos
Fil: Fong, Sheri F.T.. University of Hawaii at Manoa; Estados Unidos
Fil: Csiszar, Katalin. University of Hawaii at Manoa; Estados Unidos
Fil: Giaccia, Amato. Stanford University School of Medicine; Estados Unidos
Fil: Weninger, Wolfgang. Wistar Institute; Estados Unidos
Fil: Yamauchi, Mitsuo. University of North Carolina; Estados Unidos
Fil: Gasser, David L.. State University of Pennsylvania; Estados Unidos
Fil: Weaver, Valerie M.. State University of Pennsylvania; Estados Unidos
Materia
MATRIX CROSSLINKING
INTEGRIN SIGNALING
MECHANICAL FORCE
MAMMARY GLAND
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/104074
Acceder
id CONICETDig_1235e0055b3d267e123b0e169259ce89
oai_identifier_str oai:ri.conicet.gov.ar:11336/104074
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin SignalingLevental, Kandice R.Yu, HongmeiKass, LauraLakins, Johnathon N.Egeblad, MikalaErler, Janine T.Fong, Sheri F.T.Csiszar, KatalinGiaccia, AmatoWeninger, WolfgangYamauchi, MitsuoGasser, David L.Weaver, Valerie M.MATRIX CROSSLINKINGINTEGRIN SIGNALINGMECHANICAL FORCEMAMMARY GLANDhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Tumors are characterized by extracellular matrix (ECM) remodeling and stiffening. The importance of ECM remodeling to cancer is appreciated; the relevance of stiffening is less clear. We found that breast tumorigenesis is accompanied by collagen crosslinking, ECM stiffening, and increased focal adhesions. Induction of collagen crosslinking stiffened the ECM, promoted focal adhesions, enhanced PI3 kinase (PI3K) activity, and induced the invasion of an oncogene-initiated epithelium. Inhibition of integrin signaling repressed the invasion of a premalignant epithelium into a stiffened, crosslinked ECM and forced integrin clustering promoted focal adhesions, enhanced PI3K signaling, and induced the invasion of a premalignant epithelium. Consistently, reduction of lysyl oxidase-mediated collagen crosslinking prevented MMTV-Neu-induced fibrosis, decreased focal adhesions and PI3K activity, impeded malignancy, and lowered tumor incidence. These data show how collagen crosslinking can modulate tissue fibrosis and stiffness to force focal adhesions, growth factor signaling and breast malignancy.Fil: Levental, Kandice R.. State University of Pennsylvania; Estados UnidosFil: Yu, Hongmei. University of California; Estados UnidosFil: Kass, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; ArgentinaFil: Lakins, Johnathon N.. University of California; Estados UnidosFil: Egeblad, Mikala. University of California; Estados UnidosFil: Erler, Janine T.. Stanford University School of Medicine; Estados UnidosFil: Fong, Sheri F.T.. University of Hawaii at Manoa; Estados UnidosFil: Csiszar, Katalin. University of Hawaii at Manoa; Estados UnidosFil: Giaccia, Amato. Stanford University School of Medicine; Estados UnidosFil: Weninger, Wolfgang. Wistar Institute; Estados UnidosFil: Yamauchi, Mitsuo. University of North Carolina; Estados UnidosFil: Gasser, David L.. State University of Pennsylvania; Estados UnidosFil: Weaver, Valerie M.. State University of Pennsylvania; Estados UnidosCell Press2009-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/104074Levental, Kandice R.; Yu, Hongmei; Kass, Laura; Lakins, Johnathon N.; Egeblad, Mikala; et al.; Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling; Cell Press; Cell; 139; 5; 11-2009; 891-9060092-8674CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.cell.2009.10.027info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:31:16Zoai:ri.conicet.gov.ar:11336/104074instacron: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:34982025-10-15 14:31:16.332CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling
title Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling
spellingShingle Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling
Levental, Kandice R.
MATRIX CROSSLINKING
INTEGRIN SIGNALING
MECHANICAL FORCE
MAMMARY GLAND
title_short Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling
title_full Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling
title_fullStr Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling
title_full_unstemmed Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling
title_sort Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling
dc.creator.none.fl_str_mv Levental, Kandice R.
Yu, Hongmei
Kass, Laura
Lakins, Johnathon N.
Egeblad, Mikala
Erler, Janine T.
Fong, Sheri F.T.
Csiszar, Katalin
Giaccia, Amato
Weninger, Wolfgang
Yamauchi, Mitsuo
Gasser, David L.
Weaver, Valerie M.
author Levental, Kandice R.
author_facet Levental, Kandice R.
Yu, Hongmei
Kass, Laura
Lakins, Johnathon N.
Egeblad, Mikala
Erler, Janine T.
Fong, Sheri F.T.
Csiszar, Katalin
Giaccia, Amato
Weninger, Wolfgang
Yamauchi, Mitsuo
Gasser, David L.
Weaver, Valerie M.
author_role author
author2 Yu, Hongmei
Kass, Laura
Lakins, Johnathon N.
Egeblad, Mikala
Erler, Janine T.
Fong, Sheri F.T.
Csiszar, Katalin
Giaccia, Amato
Weninger, Wolfgang
Yamauchi, Mitsuo
Gasser, David L.
Weaver, Valerie M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv MATRIX CROSSLINKING
INTEGRIN SIGNALING
MECHANICAL FORCE
MAMMARY GLAND
topic MATRIX CROSSLINKING
INTEGRIN SIGNALING
MECHANICAL FORCE
MAMMARY GLAND
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Tumors are characterized by extracellular matrix (ECM) remodeling and stiffening. The importance of ECM remodeling to cancer is appreciated; the relevance of stiffening is less clear. We found that breast tumorigenesis is accompanied by collagen crosslinking, ECM stiffening, and increased focal adhesions. Induction of collagen crosslinking stiffened the ECM, promoted focal adhesions, enhanced PI3 kinase (PI3K) activity, and induced the invasion of an oncogene-initiated epithelium. Inhibition of integrin signaling repressed the invasion of a premalignant epithelium into a stiffened, crosslinked ECM and forced integrin clustering promoted focal adhesions, enhanced PI3K signaling, and induced the invasion of a premalignant epithelium. Consistently, reduction of lysyl oxidase-mediated collagen crosslinking prevented MMTV-Neu-induced fibrosis, decreased focal adhesions and PI3K activity, impeded malignancy, and lowered tumor incidence. These data show how collagen crosslinking can modulate tissue fibrosis and stiffness to force focal adhesions, growth factor signaling and breast malignancy.
Fil: Levental, Kandice R.. State University of Pennsylvania; Estados Unidos
Fil: Yu, Hongmei. University of California; Estados Unidos
Fil: Kass, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina
Fil: Lakins, Johnathon N.. University of California; Estados Unidos
Fil: Egeblad, Mikala. University of California; Estados Unidos
Fil: Erler, Janine T.. Stanford University School of Medicine; Estados Unidos
Fil: Fong, Sheri F.T.. University of Hawaii at Manoa; Estados Unidos
Fil: Csiszar, Katalin. University of Hawaii at Manoa; Estados Unidos
Fil: Giaccia, Amato. Stanford University School of Medicine; Estados Unidos
Fil: Weninger, Wolfgang. Wistar Institute; Estados Unidos
Fil: Yamauchi, Mitsuo. University of North Carolina; Estados Unidos
Fil: Gasser, David L.. State University of Pennsylvania; Estados Unidos
Fil: Weaver, Valerie M.. State University of Pennsylvania; Estados Unidos
description Tumors are characterized by extracellular matrix (ECM) remodeling and stiffening. The importance of ECM remodeling to cancer is appreciated; the relevance of stiffening is less clear. We found that breast tumorigenesis is accompanied by collagen crosslinking, ECM stiffening, and increased focal adhesions. Induction of collagen crosslinking stiffened the ECM, promoted focal adhesions, enhanced PI3 kinase (PI3K) activity, and induced the invasion of an oncogene-initiated epithelium. Inhibition of integrin signaling repressed the invasion of a premalignant epithelium into a stiffened, crosslinked ECM and forced integrin clustering promoted focal adhesions, enhanced PI3K signaling, and induced the invasion of a premalignant epithelium. Consistently, reduction of lysyl oxidase-mediated collagen crosslinking prevented MMTV-Neu-induced fibrosis, decreased focal adhesions and PI3K activity, impeded malignancy, and lowered tumor incidence. These data show how collagen crosslinking can modulate tissue fibrosis and stiffness to force focal adhesions, growth factor signaling and breast malignancy.
publishDate 2009
dc.date.none.fl_str_mv 2009-11
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/11336/104074
Levental, Kandice R.; Yu, Hongmei; Kass, Laura; Lakins, Johnathon N.; Egeblad, Mikala; et al.; Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling; Cell Press; Cell; 139; 5; 11-2009; 891-906
0092-8674
CONICET Digital
CONICET
url http://hdl.handle.net/11336/104074
identifier_str_mv Levental, Kandice R.; Yu, Hongmei; Kass, Laura; Lakins, Johnathon N.; Egeblad, Mikala; et al.; Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling; Cell Press; Cell; 139; 5; 11-2009; 891-906
0092-8674
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cell.2009.10.027
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell 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_ 1846082795070291968
score 13.22299

Publicaciones similares