A proteomic approach supports the clinical relevance of TAT-Cx43266-283 in glioblastoma

[EN] Glioblastoma (GBM) is the most frequent and aggressive primary brain cancer. The Src inhibitor, TAT-Cx43266-283, exerts antitumor effects in in vitro and in vivo models of GBM. Because addressing the mechanism of action is essential to translate these results to a clinical setting, in this stud...

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Detalhes bibliográficos
Autores: Gutiérrez Pelaz, Sara, Flores Hernández, Raquel, Vujic, Tatjana, Schvartz, Domitille, Álvarez Vázquez, Andrea, Ding, Yuxin, García Vicente, Laura, Belloso, Aitana, Talaverón Aguilocho, Rocío, Sánchez, Jean Charles, Tabernero Urbieta, María Aránzazu
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2024
País:España
Recursos:Universidad de Salamanca (USAL)
Repositório:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/167639
Acesso em linha:http://hdl.handle.net/10366/167639
Access Level:Acceso aberto
Palavra-chave:Brain tumors
Cell-penetrating peptides
Connexin
Glioblastoma
Proteomics
Src
3201.01 Oncología
3207.13 Oncología
2301.10 Espectroscopia de Masas
Descrição
Resumo:[EN] Glioblastoma (GBM) is the most frequent and aggressive primary brain cancer. The Src inhibitor, TAT-Cx43266-283, exerts antitumor effects in in vitro and in vivo models of GBM. Because addressing the mechanism of action is essential to translate these results to a clinical setting, in this study we carried out an unbiased proteomic approach. Data-independent acquisition mass spectrometry proteomics allowed the identification of 190 proteins whose abundance was modified by TAT-Cx43266-283. Our results were consistent with the inhibition of Src as the mechanism of action of TAT-Cx43266-283 and unveiled antitumor effectors, such as p120 catenin. Changes in the abundance of several proteins suggested that TAT-Cx43266-283 may also impact the brain microenvironment. Importantly, the proteins whose abundance was reduced by TAT-Cx43266-283 correlated with an improved GBM patient survival in clinical datasets and none of the proteins whose abundance was increased by TAT-Cx43266-283 correlated with shorter survival, supporting its use in clinical trials.

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