a short region of connexin43 reduces human glioma stem cell migration, invasion, and survival through src, pten, and fak

Summary: 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-Cx43266-283) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensin homolog in glioma stem cells (GSCs) derived from patients. Consequently, TAT-Cx43266-283 reduced GSC motility, as analyzed by time-lapse microscopy, and strongly reduced their invasive ability. Interestingly, we investigated the effects of TAT-Cx43266-283 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. : In this article, Arantxa Tabernero and colleagues show that a short region of Connexin43 exerts an important anti-tumor effect in patient-derived glioblastoma models that includes the impairment of glioma stem cell migration and invasion. This peptide targets important proteins for glioblastoma, such as Src, FAK, and PTEN, highlighting its relevance for therapeutic development against this incurable disease. Keywords: glioma stem cell, connexin, Src, PTEN, FAK, migration, invasion