Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/12663
The Netrin-1-Neogenin-1 signaling axis controls neuroblastoma cell migration via integrin-β1 and focal adhesion kinase activation.
Villanueva, Andrea A | Sanchez-Gomez, Pilar ISCIII | Muñoz-Palma, Ernesto | Puvogel, Sofía | Casas, Bárbara S | Arriagada, Cecilia | Peña-Villalobos, Isaac | Lois, Pablo | Ramírez Orellana, Manuel | Lubieniecki, Fabiana | Casco Claro, Fernando | Gallegos, Iván | Garcia-Castro, Javier ISCIII | Torres, Vicente A | Palma, Verónica
Cell Adh Migr . 2021 Dec;15(1):58-73.
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 β1 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 β1, 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 β1 and promotes neuroblastoma cell migration.
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