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

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Adhesion & Migration Pub Date : 2021-12-01 DOI:10.1080/19336918.2021.1892397

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

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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.

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Netrin-1-Neogenin-1信号轴通过整合素-β1和局灶粘附激酶的激活控制神经母细胞瘤细胞的迁移。

神经母细胞瘤是一种从神经嵴细胞祖细胞产生的高度转移性肿瘤。病灶粘附激酶（FAK）是细胞迁移的调控因子，它与受体 Neogenin-1 结合并在神经母细胞瘤中上调。在这里，我们发现Netrin-1配体与Neogenin-1结合会导致FAK自身磷酸化，并以FAK依赖的方式激活整合素β1，从而促进神经母细胞瘤细胞迁移。此外，Neogenin-1与整合素β1、FAK和Netrin-1形成复合物，在所有肿瘤阶段都能被检测到，并且是神经母细胞瘤细胞迁移所必需的。重要的是，Neogenin-1 能促进免疫缺陷小鼠模型中神经母细胞瘤的转移。综上所述，这些数据表明，Neogenin-1是一种促进转移的蛋白质，它与FAK结合，激活整合素β1，并促进神经母细胞瘤细胞的迁移。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Adhesion & Migration CELL BIOLOGY-

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

53 weeks

期刊介绍： Cell Adhesion & Migration is a multi-disciplinary, peer reviewed open access journal that focuses on the biological or pathological implications of cell-cell and cell-microenvironment interactions. The main focus of this journal is fundamental science. The journal strives to serve a broad readership by regularly publishing review articles covering specific disciplines within the field, and by publishing focused issues that provide an overview on specific topics of interest within the field. Cell Adhesion & Migration publishes relevant and timely original research, as well as authoritative overviews, commentaries, and perspectives, providing context for the work presented in Cell Adhesion & Migration and for key results published elsewhere. Original research papers may cover all topics important in the field of cell-cell and cell-matrix interactions. Cell Adhesion & Migration also publishes articles related to cell biomechanics, biomaterial, and development of related imaging technologies.