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 |
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| 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 |
| 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. |
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| ISSN: | 19315244 |
| DOI: | 10.1016/j.trsl.2024.06.001 |
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