A Short Region of Connexin43 Reduces Human Glioma Stem Cell Migration, Invasion, and Survival through Src, PTEN, and FAK

[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...

ver descrição completa

Detalhes bibliográficos
Autores: Jaraíz-Rodríguez, Myriam, Tabernero, María Dolores, González-Tablas Pimenta, María, Otero Rodríguez, Álvaro, Orfao de Matos Correia e Vale, José Alberto, Medina Jiménez, José María, Tabernero Urbieta, María Aránzazu
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2017
País:España
Recursos:Universidad de Salamanca (USAL)
Repositório:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/140751
Acesso em linha:http://hdl.handle.net/10366/140751
Access Level:Acceso aberto
Palavra-chave:Instituto de Investigación Biomédica de Salamanca
Connexin43 (CX43)
CNS
Malignant tumor
Human glioma
Stem Cell Migration
Transcellular Cell Migration
Mixed Tumor, Malignant
migración transcelular de células
tumor mixto maligno
Descrição
Resumo:[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.

Registros relacionados