A Nuclear-Directed Ribonuclease Variant Targets Cancer Stem Cells and Inhibits Migration and Invasion of Breast Cancer Cells

Despite the significant advances in cancer research made in recent years, this disease remains one of the leading causes of death worldwide. In part, this is due to the fact that after therapy, a subpopulation of self-renewing tumor cells can survive and promote cancer relapse, resistance to therapi...

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Autores: Castro Gallegos, Jessica, Tornillo, Giusy, Ceada, Gerardo, Ramos-Neble, Beatriz, Bravo Bonilla, Marlon Rolando, Ribó i Panosa, Marc, Vilanova i Brugués, Maria, Smalley, Matthew J., Benito i Mundet, Antoni
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2021
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/19919
Acesso em linha:http://hdl.handle.net/10256/19919
Access Level:Acceso aberto
Palavra-chave:Ribonucleases
Cèl·lules canceroses
Cancer cells
Càncer -- Tractament
Cancer -- Treatment
Mama -- Càncer
Breast -- Cancer
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spelling A Nuclear-Directed Ribonuclease Variant Targets Cancer Stem Cells and Inhibits Migration and Invasion of Breast Cancer CellsCastro Gallegos, JessicaTornillo, GiusyCeada, GerardoRamos-Neble, BeatrizBravo Bonilla, Marlon RolandoRibó i Panosa, MarcVilanova i Brugués, MariaSmalley, Matthew J.Benito i Mundet, AntoniRibonucleasesCèl·lules cancerosesCancer cellsCàncer -- TractamentCancer -- TreatmentMama -- CàncerBreast -- CancerDespite the significant advances in cancer research made in recent years, this disease remains one of the leading causes of death worldwide. In part, this is due to the fact that after therapy, a subpopulation of self-renewing tumor cells can survive and promote cancer relapse, resistance to therapies and metastasis. Targeting these cancer stem cells (CSCs) is therefore essential to improve the clinical outcome of cancer patients. In this sense, multi-targeted drugs may be promising agents targeting CSC-associated multifocal effects. We have previously constructed different human pancreatic ribonuclease (RNase) variants that are cytotoxic for tumor cells due to a non-classical nuclear localization signal introduced in their sequence. These cytotoxic RNases affect the expression of multiple genes involved in deregulated metabolic and signaling pathways in cancer cells and are highly cytotoxic for multidrug-resistant tumor cell lines. Here, we show that these cytotoxic nuclear-directed RNases are highly selective for tumor cell lines grown in 3D, inhibit CSCs’ development and diminish the self-renewal capacity of the CSCs population. Moreover, these human RNase variants reduce the migration and invasiveness of highly invasive breast cancer cells and downregulate N-cadherin expressionM.J.S. and G.T. are funded by Breast Cancer Now, grant number 2018NovPR1211, and Breast Cancer Research Aid. This research was funded by minECO (Spain), grant number BIO2013-43517, and by Universitat de Girona (Spain), grant number MPCU2016/18MDPI (Multidisciplinary Digital Publishing Institute)Ministerio de Economía y Competitividad (Espanya)2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/19919http://hdl.handle.net/10256/19919Cancers, 2021, vol. 13, núm. 17, p. 4350Articles publicats (D-B)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.3390/cancers13174350info:eu-repo/semantics/altIdentifier/eissn/2072-6694info:eu-repo/grantAgreement/MINECO//BIO2013-43517-RAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10256/199192026-05-29T05:05:01Z
dc.title.none.fl_str_mv A Nuclear-Directed Ribonuclease Variant Targets Cancer Stem Cells and Inhibits Migration and Invasion of Breast Cancer Cells
title A Nuclear-Directed Ribonuclease Variant Targets Cancer Stem Cells and Inhibits Migration and Invasion of Breast Cancer Cells
spellingShingle A Nuclear-Directed Ribonuclease Variant Targets Cancer Stem Cells and Inhibits Migration and Invasion of Breast Cancer Cells
Castro Gallegos, Jessica
Ribonucleases
Cèl·lules canceroses
Cancer cells
Càncer -- Tractament
Cancer -- Treatment
Mama -- Càncer
Breast -- Cancer
title_short A Nuclear-Directed Ribonuclease Variant Targets Cancer Stem Cells and Inhibits Migration and Invasion of Breast Cancer Cells
title_full A Nuclear-Directed Ribonuclease Variant Targets Cancer Stem Cells and Inhibits Migration and Invasion of Breast Cancer Cells
title_fullStr A Nuclear-Directed Ribonuclease Variant Targets Cancer Stem Cells and Inhibits Migration and Invasion of Breast Cancer Cells
title_full_unstemmed A Nuclear-Directed Ribonuclease Variant Targets Cancer Stem Cells and Inhibits Migration and Invasion of Breast Cancer Cells
title_sort A Nuclear-Directed Ribonuclease Variant Targets Cancer Stem Cells and Inhibits Migration and Invasion of Breast Cancer Cells
dc.creator.none.fl_str_mv Castro Gallegos, Jessica
Tornillo, Giusy
Ceada, Gerardo
Ramos-Neble, Beatriz
Bravo Bonilla, Marlon Rolando
Ribó i Panosa, Marc
Vilanova i Brugués, Maria
Smalley, Matthew J.
Benito i Mundet, Antoni
author Castro Gallegos, Jessica
author_facet Castro Gallegos, Jessica
Tornillo, Giusy
Ceada, Gerardo
Ramos-Neble, Beatriz
Bravo Bonilla, Marlon Rolando
Ribó i Panosa, Marc
Vilanova i Brugués, Maria
Smalley, Matthew J.
Benito i Mundet, Antoni
author_role author
author2 Tornillo, Giusy
Ceada, Gerardo
Ramos-Neble, Beatriz
Bravo Bonilla, Marlon Rolando
Ribó i Panosa, Marc
Vilanova i Brugués, Maria
Smalley, Matthew J.
Benito i Mundet, Antoni
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (Espanya)
dc.subject.none.fl_str_mv Ribonucleases
Cèl·lules canceroses
Cancer cells
Càncer -- Tractament
Cancer -- Treatment
Mama -- Càncer
Breast -- Cancer
topic Ribonucleases
Cèl·lules canceroses
Cancer cells
Càncer -- Tractament
Cancer -- Treatment
Mama -- Càncer
Breast -- Cancer
description Despite the significant advances in cancer research made in recent years, this disease remains one of the leading causes of death worldwide. In part, this is due to the fact that after therapy, a subpopulation of self-renewing tumor cells can survive and promote cancer relapse, resistance to therapies and metastasis. Targeting these cancer stem cells (CSCs) is therefore essential to improve the clinical outcome of cancer patients. In this sense, multi-targeted drugs may be promising agents targeting CSC-associated multifocal effects. We have previously constructed different human pancreatic ribonuclease (RNase) variants that are cytotoxic for tumor cells due to a non-classical nuclear localization signal introduced in their sequence. These cytotoxic RNases affect the expression of multiple genes involved in deregulated metabolic and signaling pathways in cancer cells and are highly cytotoxic for multidrug-resistant tumor cell lines. Here, we show that these cytotoxic nuclear-directed RNases are highly selective for tumor cell lines grown in 3D, inhibit CSCs’ development and diminish the self-renewal capacity of the CSCs population. Moreover, these human RNase variants reduce the migration and invasiveness of highly invasive breast cancer cells and downregulate N-cadherin expression
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
peer-reviewed
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/19919
http://hdl.handle.net/10256/19919
url http://hdl.handle.net/10256/19919
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/cancers13174350
info:eu-repo/semantics/altIdentifier/eissn/2072-6694
info:eu-repo/grantAgreement/MINECO//BIO2013-43517-R
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI (Multidisciplinary Digital Publishing Institute)
publisher.none.fl_str_mv MDPI (Multidisciplinary Digital Publishing Institute)
dc.source.none.fl_str_mv Cancers, 2021, vol. 13, núm. 17, p. 4350
Articles publicats (D-B)
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
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score 15,812429

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