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

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Názov: A proteomic approach supports the clinical relevance of TAT-Cx43266-283 in glioblastoma
Autori: Sara G. Pelaz, Raquel Flores-Hernández, Tatjana Vujic, Domitille Schvartz, Andrea Álvarez-Vázquez, Yuxin Ding, Laura García-Vicente, Aitana Belloso, Rocío Talaverón, Jean-Charles Sánchez, Arantxa Tabernero
Zdroj: Translational research, vol. 272, pp. 95-110
Informácie o vydavateľovi: Elsevier BV, 2024.
Rok vydania: 2024
Predmety: Glioblastoma/metabolism, Glioblastoma/pathology, Humans, Proteomics/methods, Brain Neoplasms/metabolism, Brain Neoplasms/pathology, Cell Line, Tumor, src-Family Kinases/metabolism, Clinical Relevance, Brain tumors, Cell-penetrating peptides, Connexin, Glioblastoma, Proteomics, Src, src-Family Kinases, Brain Neoplasms
Popis: 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.
Druh dokumentu: Article
Popis súboru: application/pdf
Jazyk: English
ISSN: 1931-5244
DOI: 10.1016/j.trsl.2024.06.001
Prístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/38876188
http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_61BEB1A329563
https://serval.unil.ch/notice/serval:BIB_61BEB1A32956
https://serval.unil.ch/resource/serval:BIB_61BEB1A32956.P001/REF.pdf
Rights: CC BY NC ND
Prístupové číslo: edsair.doi.dedup.....52a1c5b14d8c4245672cc2db0b657cfb
Databáza: OpenAIRE
Popis
Abstrakt: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.
ISSN:19315244
DOI:10.1016/j.trsl.2024.06.001