Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2023 |
| Outros Autores: | , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | https://hdl.handle.net/1822/86668 |
Resumo: | Available online 28 September 2023 |
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Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cellsTNBCMAPK/ERK cascadeMEK1siRNAExosome-mediated silencingAvailable online 28 September 2023Triple negative breast cancer (TNBC) is a highly heterogenous disease not sensitive to endocrine or HER2 therapy and standardized treatment regimens are still missing. Therefore, development of novel TNBC treatment approaches is of utmost relevance. Herein, the potential of MAPK/ERK downregulation by RNAi-based therapeutics in a panel of mesenchymal stem-like TNBC cell lines was uncovered. Our data revealed that suppression of one of the central nodes of this signaling pathway, MEK1, affects proliferation, migration, and invasion of TNBC cells, that may be explained by the reversion of the epithelial-mesenchymal transition phenotype, which is facilitated by the MMP-2/MMP-9 downregulation. Moreover, an exosome-based system was successfully generated for the siRNA loading (iExoMEK1). Our data suggested absence of modification of the physical properties and general integrity of the iExoMEK1 comparatively to the unmodified counterparts. Such exosome-mediated downregulation of MEK1 led to a tumor regression accompanied by a decrease of angiogenesis using the chick chorioallantoic-membrane model. Our results highlight the potential of the targeting of MAPK/ERK cascade as a promising therapeutic approach against TNBC.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/ BIO/04469/2020 unit. CAM and immunohistochemistry experiments have been funded by ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI - Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122); by National funds, through the Foundation for Science and Technology (FCT) - project UIDB/50026/ 2020 and UIDP/50026/2020 and by the project NORTE-01-0145- FEDER-000039, supported by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Débora Ferreira is recipient of a fellowship supported by a doctoral advanced training (call NORTE-69-2015-15) funded by the European Social Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. Débora Ferreira also acknowledges “Liga Portuguesa contra o cancro - Núcleo Regional do Norte (LPCC-NRN)” for her fellowship. The authors thank Diana Vilas Boas (CEB/University of Minho) for confocal microscopy technical support. Cátia Santos-Pereira acknowledges the PhD fellowship PD/BD/128032/2016 funded by FCT under the scope of the doctoral program in Applied and Environmental Microbiology (DP_AEM). Julieta Afonso acknowledges the Postdoctoral fellowship SFRH/BPD/116784/2016 funded by FCT. The work performed in the Kalluri Laboratory was supported by funds from UT MD Anderson Cancer Center and the Sid Richardson Foundation.info:eu-repo/semantics/publishedVersionElsevierUniversidade do MinhoFerreira, Débora Carina Gonçalves AbreuPereira, Cátia Sofia SantosCosta, MartaAfonso, Julieta Alexandra PereiraYang, SujuanHensel, JanineMcAndrews, Kathleen M.Longatto, AdhemarFernandes, RuiMelo, Joana B.Baltazar, FátimaMoreira, João N.Kalluri, RaghuRodrigues, L. R.2023-112023-11-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/86668engFerreira, Débora; Cátia S. Pereira; Costa, Marta; Afonso, Julieta; Yang, Sujuan; Hensel, Janine; McAndrews, Kathleen M.; Longatto-Filho, Adhemar; Fernandes, Rui; Melo, Joana B.; Baltazar, Fátima; Moreira, João N.; Kalluri, Raghu; Rodrigues, Lígia R., Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells. Biomaterials Advances, 154(213643), 20232772-950810.1016/j.bioadv.2023.21364337778291213643https://www.sciencedirect.com/journal/biomaterials-advancesinfo: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:RCAAP2023-12-02T01:20:43Zoai:repositorium.sdum.uminho.pt:1822/86668Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:33:33.013532Repositório 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 |
Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells |
| title |
Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells |
| spellingShingle |
Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells Ferreira, Débora Carina Gonçalves Abreu TNBC MAPK/ERK cascade MEK1 siRNA Exosome-mediated silencing |
| title_short |
Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells |
| title_full |
Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells |
| title_fullStr |
Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells |
| title_full_unstemmed |
Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells |
| title_sort |
Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells |
| author |
Ferreira, Débora Carina Gonçalves Abreu |
| author_facet |
Ferreira, Débora Carina Gonçalves Abreu Pereira, Cátia Sofia Santos Costa, Marta Afonso, Julieta Alexandra Pereira Yang, Sujuan Hensel, Janine McAndrews, Kathleen M. Longatto, Adhemar Fernandes, Rui Melo, Joana B. Baltazar, Fátima Moreira, João N. Kalluri, Raghu Rodrigues, L. R. |
| author_role |
author |
| author2 |
Pereira, Cátia Sofia Santos Costa, Marta Afonso, Julieta Alexandra Pereira Yang, Sujuan Hensel, Janine McAndrews, Kathleen M. Longatto, Adhemar Fernandes, Rui Melo, Joana B. Baltazar, Fátima Moreira, João N. Kalluri, Raghu Rodrigues, L. R. |
| author2_role |
author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidade do Minho |
| dc.contributor.author.fl_str_mv |
Ferreira, Débora Carina Gonçalves Abreu Pereira, Cátia Sofia Santos Costa, Marta Afonso, Julieta Alexandra Pereira Yang, Sujuan Hensel, Janine McAndrews, Kathleen M. Longatto, Adhemar Fernandes, Rui Melo, Joana B. Baltazar, Fátima Moreira, João N. Kalluri, Raghu Rodrigues, L. R. |
| dc.subject.por.fl_str_mv |
TNBC MAPK/ERK cascade MEK1 siRNA Exosome-mediated silencing |
| topic |
TNBC MAPK/ERK cascade MEK1 siRNA Exosome-mediated silencing |
| description |
Available online 28 September 2023 |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023-11 2023-11-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/1822/86668 |
| url |
https://hdl.handle.net/1822/86668 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Ferreira, Débora; Cátia S. Pereira; Costa, Marta; Afonso, Julieta; Yang, Sujuan; Hensel, Janine; McAndrews, Kathleen M.; Longatto-Filho, Adhemar; Fernandes, Rui; Melo, Joana B.; Baltazar, Fátima; Moreira, João N.; Kalluri, Raghu; Rodrigues, Lígia R., Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells. Biomaterials Advances, 154(213643), 2023 2772-9508 10.1016/j.bioadv.2023.213643 37778291 213643 https://www.sciencedirect.com/journal/biomaterials-advances |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Elsevier |
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Elsevier |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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