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Title

A short region of connexin43 reduces human glioma stem cell migration, invasion, and survival through Src, PTEN, and FAK

AuthorsJaraíz-Rodríguez, Myriam; Tabernero, María D.; González-Tablas, María; Otero, Álvaro; Orfao, Alberto ; Medina, Jose M.; Tabernero, Arantxa
Issue Date2017
PublisherElsevier
CitationStem Cell Reports 9(2): 451-463 (2017)
AbstractConnexin43 (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.
Publisher version (URL)https://doi.org/10.1016/j.stemcr.2017.06.007
URIhttp://hdl.handle.net/10261/169240
Identifiersdoi: 10.1016/j.stemcr.2017.06.007
e-issn: 2213-6711
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