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

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
Source :
Cell Adhesion & Migration, Vol 15, Iss 1, Pp 58-73 (2021)
Publication Year :
2021
Publisher :
Taylor & Francis Group, 2021.

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 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.

Details

Language :
English
ISSN :
19336918 and 19336926
Volume :
15
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Cell Adhesion & Migration
Publication Type :
Academic Journal
Accession number :
edsdoj.968b885eb8704c3c84ca358077c5182e
Document Type :
article
Full Text :
https://doi.org/10.1080/19336918.2021.1892397