A Short Region of Connexin43 Reduces Human Glioma Stem Cell Migration, Invasion, and Survival through Src, PTEN, and FAK
Instituto de Investigación Biomédica de Salamanca
Stem Cell Migration
Fecha de publicación
Jaraíz-Rodríguez, M., Tabernero, M. D., González-Tablas, M., Otero, A., Orfao, A., Medina, J. M., & Tabernero, A. (2017). A short region of connexin43 reduces human glioma stem cell migration, invasion, and survival through Src, PTEN, and FAK. Stem cell reports, 9(2), 451-463.
[EN] 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 onmigration and invasion. Here,weshowthat a cell-penetrating peptide based onCX43(TAT-Cx43266-283) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensinhomolog inglioma 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.
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