Snail1-dependent activation of cancer-associated fibroblast controls epithelial tumor cell invasion and metastasis.

40 p.-6 fig.

Detalles Bibliográficos
Autores: Alba-Castellón, Lorena, Olivera, Rubén, Mestre, Aida, Peña, Raúl, Herrera, Mercedes, Bonilla, Félix, Baulida, Josep, Casal, J. Ignacio, Peña Maroto, Cristina, García de Herreros, Antonio
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/158776
Acceso en línea:http://hdl.handle.net/10261/158776
Access Level:acceso abierto
Palabra clave:Snail1
PGE2
Fibroblast activation
TGF-B
Tumor invasion
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spelling Snail1-dependent activation of cancer-associated fibroblast controls epithelial tumor cell invasion and metastasis.Snail1 controls cancer-associated fibroblast action on tumor cell invasion and metastasisEMT-independent Snail1 modulation of tumor invasionAlba-Castellón, LorenaOlivera, RubénMestre, AidaPeña, RaúlHerrera, MercedesBonilla, FélixBaulida, JosepCasal, J. IgnacioPeña Maroto, CristinaGarcía de Herreros, AntonioSnail1PGE2Fibroblast activationTGF-BTumor invasion40 p.-6 fig.Snail1 transcriptional factor is essential for triggering epithelial-to-mesenchymal transition (EMT) and inducing tumor cell invasion. We report here an additional, EMTindependent action of Snail1 on tumor invasion: its expression in cancer-associated fibroblasts is necessary for enhancement by these cells on epithelial cells tumor invasion. Snail1 expression in fibroblast requires signals derived from tumor cells such as TGF-; reciprocally, in fibroblasts Snail1 organizes a complex program that favors collective invasion of epithelial cells at least in part by the secretion of diffusible signaling molecules, such as prostaglandin E2. The capability of human or murine tumor-derived cancer associated fibroblasts to promote tumor invasion is associated to Snail1 expression and obliterated by Snail1 depletion. In vivo experiments show that Snail1 depletion in mice prevents the invasion of breast tumors and epithelial tumor cells co-xenografted with Snail1-depleted fibroblasts originate tumors with lower invasion than those transplanted with control fibroblasts. Therefore, these results demonstrate that the role of Snail1 in tumor invasion is not limited to EMT but dependent on its expression in stromal fibroblasts where it orchestrates its activation and the crosstalk with epithelial tumor cells. Moreover, they point to the interference of Snail expression as a promising target for preventing the action of stromal fibroblasts on tumor progression.This work was funded by grants from Fundación Científica de la Asociación Española contra el Cáncer to AGH, JIC and FB, and Ministerio de Economía(SAF2013-48849-C2-1-R) and Fundació La Marató de TV3 (120130) to AGH. We also thank the support from Instituto Carlos III (RD12/0036/005 and RD12/0036/004,1 part of the Plan Nacional I+D+I and cofounded by the ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional-FEDER) and Generalitat de Catalunya (2014 SGR 32).Peer reviewedAmerican Association for Cancer ResearchAsociación Española Contra el CáncerMinisterio de Economía y Competitividad (España)Fundació La Marató de TV3Instituto de Salud Carlos IIIGeneralitat de CatalunyaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201820182016info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/158776reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-48849-C2-1-Rhttp://dx.doi.org/10.1158/0008-5472.CAN-16-0176Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1587762026-05-22T06:33:51Z
dc.title.none.fl_str_mv Snail1-dependent activation of cancer-associated fibroblast controls epithelial tumor cell invasion and metastasis.
Snail1 controls cancer-associated fibroblast action on tumor cell invasion and metastasis
EMT-independent Snail1 modulation of tumor invasion
title Snail1-dependent activation of cancer-associated fibroblast controls epithelial tumor cell invasion and metastasis.
spellingShingle Snail1-dependent activation of cancer-associated fibroblast controls epithelial tumor cell invasion and metastasis.
Alba-Castellón, Lorena
Snail1
PGE2
Fibroblast activation
TGF-B
Tumor invasion
title_short Snail1-dependent activation of cancer-associated fibroblast controls epithelial tumor cell invasion and metastasis.
title_full Snail1-dependent activation of cancer-associated fibroblast controls epithelial tumor cell invasion and metastasis.
title_fullStr Snail1-dependent activation of cancer-associated fibroblast controls epithelial tumor cell invasion and metastasis.
title_full_unstemmed Snail1-dependent activation of cancer-associated fibroblast controls epithelial tumor cell invasion and metastasis.
title_sort Snail1-dependent activation of cancer-associated fibroblast controls epithelial tumor cell invasion and metastasis.
dc.creator.none.fl_str_mv Alba-Castellón, Lorena
Olivera, Rubén
Mestre, Aida
Peña, Raúl
Herrera, Mercedes
Bonilla, Félix
Baulida, Josep
Casal, J. Ignacio
Peña Maroto, Cristina
García de Herreros, Antonio
author Alba-Castellón, Lorena
author_facet Alba-Castellón, Lorena
Olivera, Rubén
Mestre, Aida
Peña, Raúl
Herrera, Mercedes
Bonilla, Félix
Baulida, Josep
Casal, J. Ignacio
Peña Maroto, Cristina
García de Herreros, Antonio
author_role author
author2 Olivera, Rubén
Mestre, Aida
Peña, Raúl
Herrera, Mercedes
Bonilla, Félix
Baulida, Josep
Casal, J. Ignacio
Peña Maroto, Cristina
García de Herreros, Antonio
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Asociación Española Contra el Cáncer
Ministerio de Economía y Competitividad (España)
Fundació La Marató de TV3
Instituto de Salud Carlos III
Generalitat de Catalunya
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Snail1
PGE2
Fibroblast activation
TGF-B
Tumor invasion
topic Snail1
PGE2
Fibroblast activation
TGF-B
Tumor invasion
description 40 p.-6 fig.
publishDate 2016
dc.date.none.fl_str_mv 2016
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/158776
url http://hdl.handle.net/10261/158776
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-48849-C2-1-R
http://dx.doi.org/10.1158/0008-5472.CAN-16-0176
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Association for Cancer Research
publisher.none.fl_str_mv American Association for Cancer Research
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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