Expression of receptor activator of NFkB (RANK) drives stemness and resistance to therapy in ER+HER2- breast cancer

Detalhes bibliográficos
Autor(a) principal: Fernandes Gomes, Inês
Data de Publicação: 2020
Outros Autores: Almeida, Bernardo P. De, Dâmaso, Sara, Mansinho, André, Correia, Inês, Henriques, Sara, Duarte, Raquel, Vilhais, Guilherme, Félix, Pedro, Alves, Patrícia, Corredeira, Patrícia, Barbosa-Morais, Nuno, Costa, Luis, Casimiro, Sandra
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/54574
Resumo: © Gomes et al. Copyright: Gomes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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spelling Expression of receptor activator of NFkB (RANK) drives stemness and resistance to therapy in ER+HER2- breast cancerER+ breast cancerRANKL-RANK pathwayMetastizationResistance to chemo and hormone therapyStemness© Gomes et al. Copyright: Gomes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The role of RANKL-RANK pathway in progesterone-driven mammary carcinogenesis and triple negative breast cancer tumorigenesis has been well characterized. However, and despite evidences of the existence of RANK-positive hormone receptor (HR)-positive breast tumors, the implication of RANK expression in HR-positive breast cancers has not been addressed before. Here, we report that RANK pathway affects the expression of cell cycle regulators and decreases sensitivity to fulvestrant of estrogen receptor (ER)-positive (ER+)/HER2- breast cancer cells, MCF-7 and T47D. Moreover, RANK overexpressing cells had a staminal and mesenchymal phenotype, with decreased proliferation rate and decreased susceptibility to chemotherapy, but were more invasive in vivo. In silico analysis of the transcriptome of human breast tumors, confirmed the association between RANK expression and stem cell and mesenchymal markers in ER+HER2- tumors. Importantly, exposure of ER+HER2- cells to continuous RANK pathway activation by exogenous RANKL, in vitro and in vivo, induced a negative feedback effect, independent of RANK levels, leading to the downregulation of HR and increased resistance to hormone therapy. These results suggest that ER+HER2- RANK-positive cells may constitute an important reservoir of slow cycling, therapy-resistance cancer cells; and that RANK pathway activation is deleterious in all ER+HER2- breast cancer cells, independently of RANK levels.This project was funded by the research project PTDC/MED-ONC/28636/2017 from Fundação para a Ciência e a Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado. IG is supported by the FCT PhD grant SFRH/BD/139178/2018Impact JournalsRepositório da Universidade de LisboaFernandes Gomes, InêsAlmeida, Bernardo P. DeDâmaso, SaraMansinho, AndréCorreia, InêsHenriques, SaraDuarte, RaquelVilhais, GuilhermeFélix, PedroAlves, PatríciaCorredeira, PatríciaBarbosa-Morais, NunoCosta, LuisCasimiro, Sandra2022-09-23T14:29:32Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/54574engOncotarget. 2020 May 12;11(19):1714-172810.18632/oncotarget.275761949-2553info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:01:02Zoai:repositorio.ul.pt:10451/54574Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:05:23.432584Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Expression of receptor activator of NFkB (RANK) drives stemness and resistance to therapy in ER+HER2- breast cancer
title Expression of receptor activator of NFkB (RANK) drives stemness and resistance to therapy in ER+HER2- breast cancer
spellingShingle Expression of receptor activator of NFkB (RANK) drives stemness and resistance to therapy in ER+HER2- breast cancer
Fernandes Gomes, Inês
ER+ breast cancer
RANKL-RANK pathway
Metastization
Resistance to chemo and hormone therapy
Stemness
title_short Expression of receptor activator of NFkB (RANK) drives stemness and resistance to therapy in ER+HER2- breast cancer
title_full Expression of receptor activator of NFkB (RANK) drives stemness and resistance to therapy in ER+HER2- breast cancer
title_fullStr Expression of receptor activator of NFkB (RANK) drives stemness and resistance to therapy in ER+HER2- breast cancer
title_full_unstemmed Expression of receptor activator of NFkB (RANK) drives stemness and resistance to therapy in ER+HER2- breast cancer
title_sort Expression of receptor activator of NFkB (RANK) drives stemness and resistance to therapy in ER+HER2- breast cancer
author Fernandes Gomes, Inês
author_facet Fernandes Gomes, Inês
Almeida, Bernardo P. De
Dâmaso, Sara
Mansinho, André
Correia, Inês
Henriques, Sara
Duarte, Raquel
Vilhais, Guilherme
Félix, Pedro
Alves, Patrícia
Corredeira, Patrícia
Barbosa-Morais, Nuno
Costa, Luis
Casimiro, Sandra
author_role author
author2 Almeida, Bernardo P. De
Dâmaso, Sara
Mansinho, André
Correia, Inês
Henriques, Sara
Duarte, Raquel
Vilhais, Guilherme
Félix, Pedro
Alves, Patrícia
Corredeira, Patrícia
Barbosa-Morais, Nuno
Costa, Luis
Casimiro, Sandra
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Fernandes Gomes, Inês
Almeida, Bernardo P. De
Dâmaso, Sara
Mansinho, André
Correia, Inês
Henriques, Sara
Duarte, Raquel
Vilhais, Guilherme
Félix, Pedro
Alves, Patrícia
Corredeira, Patrícia
Barbosa-Morais, Nuno
Costa, Luis
Casimiro, Sandra
dc.subject.por.fl_str_mv ER+ breast cancer
RANKL-RANK pathway
Metastization
Resistance to chemo and hormone therapy
Stemness
topic ER+ breast cancer
RANKL-RANK pathway
Metastization
Resistance to chemo and hormone therapy
Stemness
description © Gomes et al. Copyright: Gomes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-01-01T00:00:00Z
2022-09-23T14:29:32Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/54574
url http://hdl.handle.net/10451/54574
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Oncotarget. 2020 May 12;11(19):1714-1728
10.18632/oncotarget.27576
1949-2553
dc.rights.driver.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 Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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