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
{"title":"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。","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","doi":"10.1080/19336918.2021.1892397","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":3,"journal":{"name":"ACS Applied Electronic Materials","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971226/pdf/","citationCount":"0","resultStr":"{\"title\":\"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\",\"doi\":\"10.1080/19336918.2021.1892397\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":3,\"journal\":{\"name\":\"ACS Applied Electronic Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2021-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971226/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Electronic Materials\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/19336918.2021.1892397\",\"RegionNum\":3,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, ELECTRICAL & ELECTRONIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Electronic Materials","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/19336918.2021.1892397","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, ELECTRICAL & ELECTRONIC","Score":null,"Total":0}
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.