The Netrin-1-Neogenin-1 signaling axis controls neuroblastoma cell migration via integrin-ß1 and focal adhesion kinase activation.
Cell Adh Migr
; 15(1): 58-73, 2021 12.
Article
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| MEDLINE
| ID: mdl-33724150
ABSTRACT
Neuroblastoma is a highly metastatic tumor that emerges from neural crest cell progenitors. Focal Adhesion Kinase (FAK) is a regulator of cell migration that binds to the receptor Neogenin-1 and is upregulated in neuroblastoma. Here, we show that Netrin-1 ligand binding to Neogenin-1 leads to FAK autophosphorylation and integrin ß1 activation in a FAK dependent manner, thus promoting neuroblastoma cell migration. Moreover, Neogenin-1, which was detected in all tumor stages and was required for neuroblastoma cell migration, was found in a complex with integrin ß1, FAK, and Netrin-1. Importantly, Neogenin-1 promoted neuroblastoma metastases in an immunodeficient mouse model. Taken together, these data show that Neogenin-1 is a metastasis-promoting protein that associates with FAK, activates integrin ß1 and promotes neuroblastoma cell migration.
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1
Banco de datos:
MEDLINE
Asunto principal:
Integrina beta1
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Neuroblastoma
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Animals
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En
Año:
2021
Tipo del documento:
Article