Proteomics

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DIA-MS proteomics of untreated and TAT-Cx43266-283-treated G166 GSCs


ABSTRACT: Glioblastoma (GBM) is the most frequent and aggressive primary brain cancer. Our studies have shown that the Src inhibitor, TAT-Cx43266-283, exerts antitumor effects in different preclinical models of GBM, including fresh specimens from GBM patients, and enhances survival in glioma-bearing mice. Because addressing TAT-Cx43266-283 mechanism of action is essential to translate these results to a clinical setting, in this study we carried out an unbiased proteomic approach in human glioblastoma stem cells (GSCs). Data-independent acquisition mass spectrometry proteomics allowed the identification and quantification of 6,561 proteins, of which 190 were modified by TAT-Cx43266-283. Our results are consistent with the inhibition of Src as the mechanism of action of TAT-Cx43266-283 and unveils additional crucial proteins. Altogether, this study expands the knowledge about the mechanism of action of TAT-Cx43266-283, providing a rationale for therapy combination and supporting its use in GBM clinical trials.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain, Stem Cell

DISEASE(S): Brain Cancer

SUBMITTER: Sara G. Pelaz  

LAB HEAD: Arantxa Tabernero

PROVIDER: PXD045883 | Pride | 2024-06-22

REPOSITORIES: Pride

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A proteomic approach supports the clinical relevance of TAT-Cx43<sub>266-283</sub> in glioblastoma.

Pelaz Sara G SG   Flores-Hernández Raquel R   Vujic Tatjana T   Schvartz Domitille D   Álvarez-Vázquez Andrea A   Ding Yuxin Y   García-Vicente Laura L   Belloso Aitana A   Talaverón Rocío R   Sánchez Jean-Charles JC   Tabernero Arantxa A  

Translational research : the journal of laboratory and clinical medicine 20240612


Glioblastoma (GBM) is the most frequent and aggressive primary brain cancer. The Src inhibitor, TAT-Cx43<sub>266-283</sub>, 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-Cx43<sub  ...[more]

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