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

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 au...

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Autores principales: Villanueva, Andrea A., Sanchez-Gomez, Pilar, 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, García-Castro, Javier, Torres, Vicente A., Palma, Verónica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971226/
https://www.ncbi.nlm.nih.gov/pubmed/33724150
http://dx.doi.org/10.1080/19336918.2021.1892397
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author Villanueva, Andrea A.
Sanchez-Gomez, Pilar
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
García-Castro, Javier
Torres, Vicente A.
Palma, Verónica
author_facet Villanueva, Andrea A.
Sanchez-Gomez, Pilar
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
García-Castro, Javier
Torres, Vicente A.
Palma, Verónica
author_sort Villanueva, Andrea A.
collection PubMed
description 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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spelling pubmed-79712262021-03-31 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 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 García-Castro, Javier Torres, Vicente A. Palma, Verónica Cell Adh Migr Research Paper 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. Taylor & Francis 2021-03-16 /pmc/articles/PMC7971226/ /pubmed/33724150 http://dx.doi.org/10.1080/19336918.2021.1892397 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Villanueva, Andrea A.
Sanchez-Gomez, Pilar
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
García-Castro, Javier
Torres, Vicente A.
Palma, Verónica
The Netrin-1-Neogenin-1 signaling axis controls neuroblastoma cell migration via integrin-β1 and focal adhesion kinase activation
title The Netrin-1-Neogenin-1 signaling axis controls neuroblastoma cell migration via integrin-β1 and focal adhesion kinase activation
title_full The Netrin-1-Neogenin-1 signaling axis controls neuroblastoma cell migration via integrin-β1 and focal adhesion kinase activation
title_fullStr The Netrin-1-Neogenin-1 signaling axis controls neuroblastoma cell migration via integrin-β1 and focal adhesion kinase activation
title_full_unstemmed The Netrin-1-Neogenin-1 signaling axis controls neuroblastoma cell migration via integrin-β1 and focal adhesion kinase activation
title_short The Netrin-1-Neogenin-1 signaling axis controls neuroblastoma cell migration via integrin-β1 and focal adhesion kinase activation
title_sort netrin-1-neogenin-1 signaling axis controls neuroblastoma cell migration via integrin-β1 and focal adhesion kinase activation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971226/
https://www.ncbi.nlm.nih.gov/pubmed/33724150
http://dx.doi.org/10.1080/19336918.2021.1892397
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