Connexin43 (CX43)， a protein that forms gap junction channels and hemichannels in astrocytes， is downregulated in high-grade gliomas. Its relevance for glioma therapy has been thoroughly explored; however， its positive effects on proliferation are counterbalanced by its effects on migration and invasion. Here， we show that a cell-penetrating peptide based on CX43 (TAT-Cx43) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensin homolog in glioma stem cells (GSCs) derived from patients. Consequently， TAT-Cx43 reduced GSC motility， as analyzed by time-lapse microscopy， and strongly reduced their invasive ability. Interestingly， we investigated the effects of TAT-Cx4... More
Connexin43 (CX43)， a protein that forms gap junction channels and hemichannels in astrocytes， is downregulated in high-grade gliomas. Its relevance for glioma therapy has been thoroughly explored; however， its positive effects on proliferation are counterbalanced by its effects on migration and invasion. Here， we show that a cell-penetrating peptide based on CX43 (TAT-Cx43) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensin homolog in glioma stem cells (GSCs) derived from patients. Consequently， TAT-Cx43 reduced GSC motility， as analyzed by time-lapse microscopy， and strongly reduced their invasive ability. Interestingly， we investigated the effects of TAT-Cx43 on freshly removed surgical specimens as undissociated glioblastoma blocks， which revealed a dramatic reduction in the growth， migration， and survival of these cells. In conclusion， a region of CX43 (amino acids 266-283) exerts an important anti-tumor effect in patient-derived glioblastoma models that includes impairment of GSC migration and invasion.
