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。

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
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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引用次数: 0

摘要

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。

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

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

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

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 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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CiteScore
7.20
自引率
4.30%
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567
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