A proteomic approach supports the clinical relevance of TAT-Cx43 in glioblastoma.

Glioblastoma (GBM) is the most frequent and aggressive primary brain cancer. The Src inhibitor, TAT-Cx43, 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.

Src: coordinating metabolism in cancer.

Metabolism must be tightly regulated to fulfil the dynamic requirements of cancer cells during proliferation, migration, stemness and differentiation. Src is a node of several signals involved in many of these biological processes, and it is also an important regulator of cell metabolism. Glucose uptake, glycolysis, the pentose-phosphate pathway and oxidative phosphorylation are among the metabolic pathways that can be regulated by Src.

Impairment of Autophagic Flux Participates in the Antitumor Effects of TAT-Cx43 in Glioblastoma Stem Cells.

Autophagy is a physiological process by which various damaged or non-essential cytosolic components are recycled, contributing to cell survival under stress conditions. In cancer, autophagy can have antitumor or protumor effects depending on the developmental stage. Here, we use Western blotting, immunochemistry, and transmission electron microscopy to demonstrate that the antitumor peptide TAT-Cx43, a c-Src inhibitor, blocks autophagic flux in glioblastoma stem cells (GSCs) under basal and nutrient-deprived conditions.

Targeting metabolic plasticity in glioma stem cells in vitro and in vivo through specific inhibition of c-Src by TAT-Cx43.

Background: Glioblastoma is the most aggressive primary brain tumour and has a very poor prognosis. Inhibition of c-Src activity in glioblastoma stem cells (GSCs, responsible for glioblastoma lethality) and primary glioblastoma cells by the peptide TAT-Cx43 reduces tumorigenicity, and boosts survival in preclinical models. Because c-Src can modulate cell metabolism and several reports revealed poor clinical efficacy of various antitumoral drugs due to metabolic rewiring in cancer cells, here we explored the inhibition of advantageous GSC metabolic plasticity by the c-Src inhibitor TAT-Cx43.

Connexin43 peptide, TAT-Cx43266-283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivo.

Background: Malignant gliomas are the most frequent primary brain tumors and remain among the most incurable cancers. Although the role of the gap junction protein, connexin43 (Cx43), has been deeply investigated in malignant gliomas, no compounds have been reported with the ability to recapitulate the tumor suppressor properties of this protein in in vivo glioma models.

Methods: TAT-Cx43266-283 a cell-penetrating peptide which mimics the effect of Cx43 on c-Src inhibition, was studied in orthotopic immunocompetent and immunosuppressed models of glioma.

Identification of potassium channel proteins Kv7.2/7.3 as common partners of the dopamine and glutamate transporters DAT and GLT-1.

Dopamine and glutamate transporters (DAT and GLT-1, respectively) share some biophysical characteristics, as both are secondary active carriers coupled to electrochemical ion gradients. In order to identify common or specific components of their respective proteomes, we performed a proximity labelling assay (BioID) in the hippocampal cell line HT22. While most of the identified proteins were specific for each transporter (and will be analyzed elsewhere), we detected two membrane proteins in the shared interactome of GLT-1 and DAT: the transmembrane protein 263 (Tmem263) and the potassium channel protein Kv7.