Netrin-1-induced activation of Notch signaling mediates glioblastoma cell invasion.
J Cell Sci
; 126(Pt 11): 2459-69, 2013 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-23549787
ABSTRACT
Glioblastoma multiforme is an aggressively invasive human brain cancer, which lacks effective treatment. The axonal guidance protein, netrin-1, is overexpressed in glioblastoma tumor biopsies. In Matrigel invasion assays we observed that experimental overexpression of netrin-1 increased cell invasiveness and its downregulation decreased invasiveness. Using tandem affinity purification and mass spectrometry protein identification we found that netrin-1 forms a complex with both Notch2 and Jagged1. Recombinant netrin-1 colocalized with Jagged1 and Notch2 at the cell surface and was also present in the intracellular vesicles with Jagged1, but not with Notch2. Netrin-1 activated Notch signaling and subsequent glioblastoma cell invasion. Interestingly, the recombinant central domain of netrin-1 counteracted the effects of the full-length netrin-1 it inhibited glioblastoma cell invasion and Notch activation by retaining the Notch signaling complex at the cell surface. This finding may give rise to therapeutic applications. These results reveal a new mechanism leading to glioblastoma cell invasion, in which netrin-1 activates Notch signaling.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas de Unión al Calcio
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Transducción de Señal
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Glioblastoma
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Proteínas Supresoras de Tumor
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Péptidos y Proteínas de Señalización Intercelular
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Receptor Notch2
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Proteínas de la Membrana
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Factores de Crecimiento Nervioso
Tipo de estudio:
Guideline
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Cell Sci
Año:
2013
Tipo del documento:
Article
País de afiliación:
Finlandia