Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/86668
Título: | Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells |
Autor(es): | 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. |
Palavras-chave: | TNBC MAPK/ERK cascade MEK1 siRNA Exosome-mediated silencing |
Data: | Nov-2023 |
Editora: | Elsevier 1 |
Revista: | Biomaterials Advances |
Citação: | 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 |
Resumo(s): | Triple 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. |
Tipo: | Artigo |
Descrição: | Available online 28 September 2023 |
URI: | https://hdl.handle.net/1822/86668 |
DOI: | 10.1016/j.bioadv.2023.213643 |
e-ISSN: | 2772-9508 |
Versão da editora: | https://www.sciencedirect.com/journal/biomaterials-advances |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
---|---|---|---|---|
document_56440_1.pdf | 7,91 MB | Adobe PDF | Ver/Abrir |