Unknown

Dataset Information

0

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


ABSTRACT: 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.

SUBMITTER: Jaraiz-Rodriguez M 

PROVIDER: S-EPMC5549880 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Jaraíz-Rodríguez Myriam M   Tabernero Ma Dolores MD   González-Tablas María M   Otero Alvaro A   Orfao Alberto A   Medina Jose M JM   Tabernero Arantxa A  

Stem cell reports 20170714 2


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<sub>266-283</sub>) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensin homolog in glioma  ...[more]

Similar Datasets

| S-EPMC8417031 | biostudies-literature
| S-EPMC5226550 | biostudies-literature
| S-EPMC4454304 | biostudies-literature
| S-EPMC3958421 | biostudies-literature
| S-EPMC5288227 | biostudies-literature
| S-EPMC2953057 | biostudies-literature
| S-EPMC6893313 | biostudies-literature
| S-EPMC4627804 | biostudies-literature
| S-EPMC5522338 | biostudies-literature
| S-EPMC5410254 | biostudies-literature