Musashi-1 Enhances Glioblastoma Cell Migration and Cytoskeletal Dynamics through Translational Inhibition of Tensin3

Abstract The RNA-binding protein Musashi-1 (MSI1) exerts essential roles in multiple cellular functions, such as maintenance of self-renewal and pluripotency of stem cells. MSI1 overexpression has been observed in several tumor tissues, including glioblastoma (GBM), and is considered as a well-estab...

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Autores principales:	Hsiao-Yun Chen, Liang-Ting Lin, Mong-Lien Wang, Benoit Laurent, Chih-Hung Hsu, Chih-Ming Pan, Wan-Ru Jiang, Pau-Yuan Chen, Hsin-I Ma, Yi-Wei Chen, Pin-I Huang, Arthur Chiou, Shih-Hwa Chiou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9f683ec5fdf74fcb8deada41e17d94dd
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spelling	oai:doaj.org-article:9f683ec5fdf74fcb8deada41e17d94dd2021-12-02T11:52:18ZMusashi-1 Enhances Glioblastoma Cell Migration and Cytoskeletal Dynamics through Translational Inhibition of Tensin310.1038/s41598-017-09504-72045-2322https://doaj.org/article/9f683ec5fdf74fcb8deada41e17d94dd2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09504-7https://doaj.org/toc/2045-2322Abstract The RNA-binding protein Musashi-1 (MSI1) exerts essential roles in multiple cellular functions, such as maintenance of self-renewal and pluripotency of stem cells. MSI1 overexpression has been observed in several tumor tissues, including glioblastoma (GBM), and is considered as a well-established marker for tumor metastasis and recurrence. However, the molecular mechanisms by which MSI1 regulates cell migration are still undetermined. Here we reported that MSI1 alters cell morphology, promotes cell migration, and increases viscoelasticity of GBM cells. We also found that MSI1 directly binds to the 3′UTR of Tensin 3 (TNS3) mRNA, a negative regulator of cell migration, to inhibit its translation. Additionally, we identified that RhoA-GTP could be a potential regulator in MSI1/TNS3-mediated cell migration and morphological changes. In a xenograft animal model, high expression ratio of MSI1 to TNS3 enhanced GBM tumor migration. We also confirmed that MSI1 and TNS3 expressions are mutually exclusive in migratory tumor lesions, and GBM patients with MSI1high/TNS3low pattern tend to have poor clinical outcome. Taken together, our findings suggested a critical role of MSI1-TNS3 axis in regulating GBM migration and highlighted that the ratio of MSI1/TNS3 could predict metastatic and survival outcome of GBM patients.Hsiao-Yun ChenLiang-Ting LinMong-Lien WangBenoit LaurentChih-Hung HsuChih-Ming PanWan-Ru JiangPau-Yuan ChenHsin-I MaYi-Wei ChenPin-I HuangArthur ChiouShih-Hwa ChiouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hsiao-Yun Chen Liang-Ting Lin Mong-Lien Wang Benoit Laurent Chih-Hung Hsu Chih-Ming Pan Wan-Ru Jiang Pau-Yuan Chen Hsin-I Ma Yi-Wei Chen Pin-I Huang Arthur Chiou Shih-Hwa Chiou Musashi-1 Enhances Glioblastoma Cell Migration and Cytoskeletal Dynamics through Translational Inhibition of Tensin3
description	Abstract The RNA-binding protein Musashi-1 (MSI1) exerts essential roles in multiple cellular functions, such as maintenance of self-renewal and pluripotency of stem cells. MSI1 overexpression has been observed in several tumor tissues, including glioblastoma (GBM), and is considered as a well-established marker for tumor metastasis and recurrence. However, the molecular mechanisms by which MSI1 regulates cell migration are still undetermined. Here we reported that MSI1 alters cell morphology, promotes cell migration, and increases viscoelasticity of GBM cells. We also found that MSI1 directly binds to the 3′UTR of Tensin 3 (TNS3) mRNA, a negative regulator of cell migration, to inhibit its translation. Additionally, we identified that RhoA-GTP could be a potential regulator in MSI1/TNS3-mediated cell migration and morphological changes. In a xenograft animal model, high expression ratio of MSI1 to TNS3 enhanced GBM tumor migration. We also confirmed that MSI1 and TNS3 expressions are mutually exclusive in migratory tumor lesions, and GBM patients with MSI1high/TNS3low pattern tend to have poor clinical outcome. Taken together, our findings suggested a critical role of MSI1-TNS3 axis in regulating GBM migration and highlighted that the ratio of MSI1/TNS3 could predict metastatic and survival outcome of GBM patients.
format	article
author	Hsiao-Yun Chen Liang-Ting Lin Mong-Lien Wang Benoit Laurent Chih-Hung Hsu Chih-Ming Pan Wan-Ru Jiang Pau-Yuan Chen Hsin-I Ma Yi-Wei Chen Pin-I Huang Arthur Chiou Shih-Hwa Chiou
author_facet	Hsiao-Yun Chen Liang-Ting Lin Mong-Lien Wang Benoit Laurent Chih-Hung Hsu Chih-Ming Pan Wan-Ru Jiang Pau-Yuan Chen Hsin-I Ma Yi-Wei Chen Pin-I Huang Arthur Chiou Shih-Hwa Chiou
author_sort	Hsiao-Yun Chen
title	Musashi-1 Enhances Glioblastoma Cell Migration and Cytoskeletal Dynamics through Translational Inhibition of Tensin3
title_short	Musashi-1 Enhances Glioblastoma Cell Migration and Cytoskeletal Dynamics through Translational Inhibition of Tensin3
title_full	Musashi-1 Enhances Glioblastoma Cell Migration and Cytoskeletal Dynamics through Translational Inhibition of Tensin3
title_fullStr	Musashi-1 Enhances Glioblastoma Cell Migration and Cytoskeletal Dynamics through Translational Inhibition of Tensin3
title_full_unstemmed	Musashi-1 Enhances Glioblastoma Cell Migration and Cytoskeletal Dynamics through Translational Inhibition of Tensin3
title_sort	musashi-1 enhances glioblastoma cell migration and cytoskeletal dynamics through translational inhibition of tensin3
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9f683ec5fdf74fcb8deada41e17d94dd
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Musashi-1 Enhances Glioblastoma Cell Migration and Cytoskeletal Dynamics through Translational Inhibition of Tensin3

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