Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells

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dc.citation.articleNumber213643en_US
dc.citation.journalTitleBiomaterials Advancesen_US
dc.citation.volumeNumber154en_US
dc.contributor.authorFerreira, Déboraen_US
dc.contributor.authorSantos-Pereira, Cátiaen_US
dc.contributor.authorCosta, Martaen_US
dc.contributor.authorAfonso, Julietaen_US
dc.contributor.authorYang, Sujuanen_US
dc.contributor.authorHensel, Janineen_US
dc.contributor.authorMcAndrews, Kathleen M.en_US
dc.contributor.authorLongatto-Filho, Adhemaren_US
dc.contributor.authorFernandes, Ruien_US
dc.contributor.authorMelo, Joana B.en_US
dc.contributor.authorBaltazar, Fátimaen_US
dc.contributor.authorMoreira, João N.en_US
dc.contributor.authorKalluri, Raghuen_US
dc.contributor.authorRodrigues, Ligia R.en_US
dc.date.accessioned2024-05-08T18:56:09Zen_US
dc.date.available2024-05-08T18:56:09Zen_US
dc.date.issued2023en_US
dc.description.abstractTriple 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.en_US
dc.identifier.citationFerreira, D., Santos-Pereira, C., Costa, M., Afonso, J., Yang, S., Hensel, J., McAndrews, K. M., Longatto-Filho, A., Fernandes, R., Melo, J. B., Baltazar, F., Moreira, J. N., Kalluri, R., & Rodrigues, L. R. (2023). Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells. Biomaterials Advances, 154, 213643. https://doi.org/10.1016/j.bioadv.2023.213643en_US
dc.identifier.digital1-s20-S2772950823003667-mainen_US
dc.identifier.doihttps://doi.org/10.1016/j.bioadv.2023.213643en_US
dc.identifier.urihttps://hdl.handle.net/1911/115662en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution-NonCommercial (CC BY-NC) license. Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/en_US
dc.titleExosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cellsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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