RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness

Rank signaling enhances stemness in mouse and human mammary epithelial cells (MECs) and mediates mammary tumor initiation. Mammary tumors initiated by oncogenes or carcinogen exposure display high levels of Rank and Rank pathway inhibitors have emerged as a new strategy for breast cancer prevention...

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Autores: Benítez, Sandra, Cordero, Alex, Santamaría, Patricia G., Redondo Pedraza, Jaime, Rocha, Ana S., Collado-Solé, Alejandro, Jimenez, Maria, Sanz Moreno, Adrian, Yoldi, Guillermo, Santos, Juliana C., Benedictis, Ilaria De, Gómez Aleza, Clara, Silva Álvarez, Sabela Da, Troulé, Kevin, Gómez López, Gonzalo, Alcazar, Noelia, Palmero, Ignacio, Collado, Manuel, Serrano Marugán, Manuel, González Suárez, Eva
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/177852
Acceso en línea:https://hdl.handle.net/2445/177852
Access Level:acceso abierto
Palabra clave:Càncer de mama
Metàstasi
Cicle cel·lular
Breast cancer
Metastasis
Cell cycle
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spelling RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressivenessBenítez, SandraCordero, AlexSantamaría, Patricia G.Redondo Pedraza, JaimeRocha, Ana S.Collado-Solé, AlejandroJimenez, MariaSanz Moreno, AdrianYoldi, GuillermoSantos, Juliana C.Benedictis, Ilaria DeGómez Aleza, ClaraSilva Álvarez, Sabela DaTroulé, KevinGómez López, GonzaloAlcazar, NoeliaPalmero, IgnacioCollado, ManuelSerrano Marugán, ManuelGonzález Suárez, EvaCàncer de mamaMetàstasiCicle cel·lularBreast cancerMetastasisCell cycleRank signaling enhances stemness in mouse and human mammary epithelial cells (MECs) and mediates mammary tumor initiation. Mammary tumors initiated by oncogenes or carcinogen exposure display high levels of Rank and Rank pathway inhibitors have emerged as a new strategy for breast cancer prevention and treatment. Here, we show that ectopic Rank expression in the mammary epithelia unexpectedly delays tumor onset and reduces tumor incidence in the oncogene-driven Neu and PyMT models. Mechanistically, we have found that ectopic expression of Rank or exposure to Rankl induces senescence, even in the absence of other oncogenic mutations. Rank leads to DNA damage and senescence through p16/p19. Moreover, RANK-induced senescence is essential for Rank-driven stemness, and although initially translates into delayed tumor growth, eventually promotes tumor progression and metastasis. We uncover a dual role for Rank in the mammary epithelia: Rank induces senescence and stemness, delaying tumor initiation but increasing tumor aggressiveness.Elsevier Inc.2021202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion15 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/177852Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1016/j.devcel.2021.04.022Developmental Cell, 2021, vol. 56https://doi.org/10.1016/j.devcel.2021.04.022info:eu-repo/grantAgreement/EC/H2020/682935cc by-nc-nd (c) Benítez et al., 2021http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1778522026-05-29T05:05:01Z
dc.title.none.fl_str_mv RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness
title RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness
spellingShingle RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness
Benítez, Sandra
Càncer de mama
Metàstasi
Cicle cel·lular
Breast cancer
Metastasis
Cell cycle
title_short RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness
title_full RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness
title_fullStr RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness
title_full_unstemmed RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness
title_sort RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness
dc.creator.none.fl_str_mv Benítez, Sandra
Cordero, Alex
Santamaría, Patricia G.
Redondo Pedraza, Jaime
Rocha, Ana S.
Collado-Solé, Alejandro
Jimenez, Maria
Sanz Moreno, Adrian
Yoldi, Guillermo
Santos, Juliana C.
Benedictis, Ilaria De
Gómez Aleza, Clara
Silva Álvarez, Sabela Da
Troulé, Kevin
Gómez López, Gonzalo
Alcazar, Noelia
Palmero, Ignacio
Collado, Manuel
Serrano Marugán, Manuel
González Suárez, Eva
author Benítez, Sandra
author_facet Benítez, Sandra
Cordero, Alex
Santamaría, Patricia G.
Redondo Pedraza, Jaime
Rocha, Ana S.
Collado-Solé, Alejandro
Jimenez, Maria
Sanz Moreno, Adrian
Yoldi, Guillermo
Santos, Juliana C.
Benedictis, Ilaria De
Gómez Aleza, Clara
Silva Álvarez, Sabela Da
Troulé, Kevin
Gómez López, Gonzalo
Alcazar, Noelia
Palmero, Ignacio
Collado, Manuel
Serrano Marugán, Manuel
González Suárez, Eva
author_role author
author2 Cordero, Alex
Santamaría, Patricia G.
Redondo Pedraza, Jaime
Rocha, Ana S.
Collado-Solé, Alejandro
Jimenez, Maria
Sanz Moreno, Adrian
Yoldi, Guillermo
Santos, Juliana C.
Benedictis, Ilaria De
Gómez Aleza, Clara
Silva Álvarez, Sabela Da
Troulé, Kevin
Gómez López, Gonzalo
Alcazar, Noelia
Palmero, Ignacio
Collado, Manuel
Serrano Marugán, Manuel
González Suárez, Eva
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer de mama
Metàstasi
Cicle cel·lular
Breast cancer
Metastasis
Cell cycle
topic Càncer de mama
Metàstasi
Cicle cel·lular
Breast cancer
Metastasis
Cell cycle
description Rank signaling enhances stemness in mouse and human mammary epithelial cells (MECs) and mediates mammary tumor initiation. Mammary tumors initiated by oncogenes or carcinogen exposure display high levels of Rank and Rank pathway inhibitors have emerged as a new strategy for breast cancer prevention and treatment. Here, we show that ectopic Rank expression in the mammary epithelia unexpectedly delays tumor onset and reduces tumor incidence in the oncogene-driven Neu and PyMT models. Mechanistically, we have found that ectopic expression of Rank or exposure to Rankl induces senescence, even in the absence of other oncogenic mutations. Rank leads to DNA damage and senescence through p16/p19. Moreover, RANK-induced senescence is essential for Rank-driven stemness, and although initially translates into delayed tumor growth, eventually promotes tumor progression and metastasis. We uncover a dual role for Rank in the mammary epithelia: Rank induces senescence and stemness, delaying tumor initiation but increasing tumor aggressiveness.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/177852
url https://hdl.handle.net/2445/177852
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.devcel.2021.04.022
Developmental Cell, 2021, vol. 56
https://doi.org/10.1016/j.devcel.2021.04.022
info:eu-repo/grantAgreement/EC/H2020/682935
dc.rights.none.fl_str_mv cc by-nc-nd (c) Benítez et al., 2021
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) Benítez et al., 2021
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 15 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Inc.
publisher.none.fl_str_mv Elsevier Inc.
dc.source.none.fl_str_mv Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869404466002788352
score 15.812429

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