RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation

In estrogen receptor-negative breast cancer patients, metastatic relapse usually occurs in the lung and is responsible for the fatal outcome of the disease. Thus, a better understanding of the biology of metastasis is needed. In particular, biomarkers to identify patients that are at risk of lung me...

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Autores: Morales, Mónica, Arenas, Enrique J., Urosevic, Jelena, Guiu, Marc, Fernández, Esther, Planet, Evarist, Fenwick, Robert Bryn, Fernández Ruiz, Sonia, Salvatella, Xavier, Reverter, David, Carracedo Pérez, Arkaitz, Massagué, Joan, Gomis, Roger R
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/16429
Acceso en línea:http://hdl.handle.net/10810/16429
Access Level:acceso abierto
Palabra clave:breast cancer
lung metastasis
metastasis suppressor
epithelial mesenchymal transition
stem-cells
aldehyde dehydrogenase
expression profiles
tumors
gene
identification
dissemination
GATA-3
beta
MOLECULAR MEDICINE
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oai_identifier_str oai:addi.ehu.eus:10810/16429
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repository_id_str
spelling RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiationMorales, MónicaArenas, Enrique J.Urosevic, JelenaGuiu, MarcFernández, EstherPlanet, EvaristFenwick, Robert BrynFernández Ruiz, SoniaSalvatella, XavierReverter, DavidCarracedo Pérez, ArkaitzMassagué, JoanGomis, Roger Rbreast cancerlung metastasismetastasis suppressorepithelial mesenchymal transitionstem-cellsaldehyde dehydrogenaseexpression profilestumorsgeneidentificationdisseminationGATA-3betaMOLECULAR MEDICINEIn estrogen receptor-negative breast cancer patients, metastatic relapse usually occurs in the lung and is responsible for the fatal outcome of the disease. Thus, a better understanding of the biology of metastasis is needed. In particular, biomarkers to identify patients that are at risk of lung metastasis could open the avenue for new therapeutic opportunities. Here we characterize the biological activity of RARRES3, a new metastasis suppressor gene whose reduced expression in the primary breast tumors identifies a subgroup of patients more likely to develop lung metastasis. We show that RARRES3 downregulation engages metastasis-initiating capabilities by facilitating adhesion of the tumor cells to the lung parenchyma. In addition, impaired tumor cell differentiation due to the loss of RARRES3 phospholipase A1/A2 activity also contributes to lung metastasis. Our results establish RARRES3 downregulation as a potential biomarker to identify patients at high risk of lung metastasis who might benefit from a differentiation treatment in the adjuvant programme.We would like to thank the Functional Genomics, Microscopy, and Cytometry core facilities of IRB Barcelona, and the UB. We thank C. Caelles for the 3AOX-luc construct. We thank Angel Nebreda for his scientific suggestions. EJA is supported by "La Caixa" PhD fellowship programme, and JU is a Juan de la Cierva Researcher (MICINN). JM is a Howard Hughes investigator. The work of A. C. and S.F-R is supported by the Ramon y Cajal award to AC (Spanish Ministry of Education) and the ERC (336343). JM was supported by HHMI. RRG and XS are ICREA Research Professors (Institucio Catalana de Recerca i Estudis Avancats). Support and structural funds were provided by the Associacion Espanola Contra el Cancer (AECC), Fundacion BBVA, Generalitat de Catalunya (2009 SGR 1429), and Spanish Ministerio de Ciencia e Innovacion (MICINN) (SAF2010-21171) to RRG.Wiley Blackwell201520152014info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/16429reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoInglésinfo:eu-repo/grantAgreement/MICINN/SAF2010-21171/http://embomolmed.embopress.org/content/6/7/865info:eu-repo/semantics/openAccessLicense: This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.oai:addi.ehu.eus:10810/164292026-06-18T09:23:17Z
dc.title.none.fl_str_mv RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation
title RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation
spellingShingle RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation
Morales, Mónica
breast cancer
lung metastasis
metastasis suppressor
epithelial mesenchymal transition
stem-cells
aldehyde dehydrogenase
expression profiles
tumors
gene
identification
dissemination
GATA-3
beta
MOLECULAR MEDICINE
title_short RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation
title_full RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation
title_fullStr RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation
title_full_unstemmed RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation
title_sort RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation
dc.creator.none.fl_str_mv Morales, Mónica
Arenas, Enrique J.
Urosevic, Jelena
Guiu, Marc
Fernández, Esther
Planet, Evarist
Fenwick, Robert Bryn
Fernández Ruiz, Sonia
Salvatella, Xavier
Reverter, David
Carracedo Pérez, Arkaitz
Massagué, Joan
Gomis, Roger R
author Morales, Mónica
author_facet Morales, Mónica
Arenas, Enrique J.
Urosevic, Jelena
Guiu, Marc
Fernández, Esther
Planet, Evarist
Fenwick, Robert Bryn
Fernández Ruiz, Sonia
Salvatella, Xavier
Reverter, David
Carracedo Pérez, Arkaitz
Massagué, Joan
Gomis, Roger R
author_role author
author2 Arenas, Enrique J.
Urosevic, Jelena
Guiu, Marc
Fernández, Esther
Planet, Evarist
Fenwick, Robert Bryn
Fernández Ruiz, Sonia
Salvatella, Xavier
Reverter, David
Carracedo Pérez, Arkaitz
Massagué, Joan
Gomis, Roger R
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv breast cancer
lung metastasis
metastasis suppressor
epithelial mesenchymal transition
stem-cells
aldehyde dehydrogenase
expression profiles
tumors
gene
identification
dissemination
GATA-3
beta
MOLECULAR MEDICINE
topic breast cancer
lung metastasis
metastasis suppressor
epithelial mesenchymal transition
stem-cells
aldehyde dehydrogenase
expression profiles
tumors
gene
identification
dissemination
GATA-3
beta
MOLECULAR MEDICINE
description In estrogen receptor-negative breast cancer patients, metastatic relapse usually occurs in the lung and is responsible for the fatal outcome of the disease. Thus, a better understanding of the biology of metastasis is needed. In particular, biomarkers to identify patients that are at risk of lung metastasis could open the avenue for new therapeutic opportunities. Here we characterize the biological activity of RARRES3, a new metastasis suppressor gene whose reduced expression in the primary breast tumors identifies a subgroup of patients more likely to develop lung metastasis. We show that RARRES3 downregulation engages metastasis-initiating capabilities by facilitating adhesion of the tumor cells to the lung parenchyma. In addition, impaired tumor cell differentiation due to the loss of RARRES3 phospholipase A1/A2 activity also contributes to lung metastasis. Our results establish RARRES3 downregulation as a potential biomarker to identify patients at high risk of lung metastasis who might benefit from a differentiation treatment in the adjuvant programme.
publishDate 2014
dc.date.none.fl_str_mv 2014
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/16429
url http://hdl.handle.net/10810/16429
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MICINN/SAF2010-21171/
http://embomolmed.embopress.org/content/6/7/865
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell
publisher.none.fl_str_mv Wiley Blackwell
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869425137932042241
score 15,300719

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