The Netrin-1-Neogenin-1 signaling axis controls neuroblastoma cell migration via integrin-β1 and focal adhesion kinase activation

• Main Authors: Andrea A. Villanueva, Pilar Sanchez-Gomez, Ernesto Muñoz-Palma, Sofía Puvogel, Bárbara S. Casas, Cecilia Arriagada, Isaac Peña-Villalobos, Pablo Lois, Manuel Ramírez Orellana, Fabiana Lubieniecki, Fernando Casco Claro, Iván Gallegos, Javier García-Castro, Vicente A. Torres, Verónica Palma
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2021-01-01
• Series: Cell Adhesion & Migration
• Subjects: netrin-1; neogenin-1; integrin-β1 activation; fak; cell migration; metastasis; neuroblastoma
• Online Access: http://dx.doi.org/10.1080/19336918.2021.1892397

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.