Overexpression of RASD1 inhibits glioma cell migration/invasion and inactivates the AKT/mTOR signaling pathway

Abstract The RAS signaling pathway is hyperactive in malignant glioma due to overexpression and/or increased activity. A previous study identified that RASD1, a member of the RAS superfamily of small G-proteins, is a significantly dysregulated gene in oligodendroglial tumors that responded to chemot...

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Autores principales:	Shangfeng Gao, Lei Jin, Guangping Liu, Peng Wang, Zonghan Sun, Yujia Cao, Hengliang Shi, Xuejiao Liu, Qiong Shi, Xiuping Zhou, Rutong Yu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/686553a62acc4c4abcac280a47e034f8
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spelling	oai:doaj.org-article:686553a62acc4c4abcac280a47e034f82021-12-02T12:30:16ZOverexpression of RASD1 inhibits glioma cell migration/invasion and inactivates the AKT/mTOR signaling pathway10.1038/s41598-017-03612-02045-2322https://doaj.org/article/686553a62acc4c4abcac280a47e034f82017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03612-0https://doaj.org/toc/2045-2322Abstract The RAS signaling pathway is hyperactive in malignant glioma due to overexpression and/or increased activity. A previous study identified that RASD1, a member of the RAS superfamily of small G-proteins, is a significantly dysregulated gene in oligodendroglial tumors that responded to chemotherapy. However, the role and mechanism of RASD1 in the progression of human glioma remain largely unknown. In the present study, by analyzing a public genomics database, we found that high levels of RASD1 predicted good survival of astrocytoma patients. We thus established lentivirus-mediated RASD1-overexpressing glioma cells and found that overexpressing RASD1 had no significant effects on glioma cell proliferation. However, the overexpression of RASD1 inhibited glioma cell migration and invasion. In the intracranial glioma xenograft model, the overexpression of RASD1 significantly reduced the number of tumor cells invading into the surrounding tissues without affecting the tumor size. An intracellular signaling array revealed that the phosphorylation of both AKT and the S6 ribosomal protein significantly decreased with RASD1 overexpression in glioma cells. Interestingly, RASD1 protein levels were significantly higher in grade II and grade III astrocytoma tissues than in nontumorous brain tissues. These findings suggest that the upregulation of RASD1 in glioma tissues may play an inhibitory role in tumor expansion, possibly through inactivating the AKT/mTOR signaling pathway.Shangfeng GaoLei JinGuangping LiuPeng WangZonghan SunYujia CaoHengliang ShiXuejiao LiuQiong ShiXiuping ZhouRutong YuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shangfeng Gao Lei Jin Guangping Liu Peng Wang Zonghan Sun Yujia Cao Hengliang Shi Xuejiao Liu Qiong Shi Xiuping Zhou Rutong Yu Overexpression of RASD1 inhibits glioma cell migration/invasion and inactivates the AKT/mTOR signaling pathway
description	Abstract The RAS signaling pathway is hyperactive in malignant glioma due to overexpression and/or increased activity. A previous study identified that RASD1, a member of the RAS superfamily of small G-proteins, is a significantly dysregulated gene in oligodendroglial tumors that responded to chemotherapy. However, the role and mechanism of RASD1 in the progression of human glioma remain largely unknown. In the present study, by analyzing a public genomics database, we found that high levels of RASD1 predicted good survival of astrocytoma patients. We thus established lentivirus-mediated RASD1-overexpressing glioma cells and found that overexpressing RASD1 had no significant effects on glioma cell proliferation. However, the overexpression of RASD1 inhibited glioma cell migration and invasion. In the intracranial glioma xenograft model, the overexpression of RASD1 significantly reduced the number of tumor cells invading into the surrounding tissues without affecting the tumor size. An intracellular signaling array revealed that the phosphorylation of both AKT and the S6 ribosomal protein significantly decreased with RASD1 overexpression in glioma cells. Interestingly, RASD1 protein levels were significantly higher in grade II and grade III astrocytoma tissues than in nontumorous brain tissues. These findings suggest that the upregulation of RASD1 in glioma tissues may play an inhibitory role in tumor expansion, possibly through inactivating the AKT/mTOR signaling pathway.
format	article
author	Shangfeng Gao Lei Jin Guangping Liu Peng Wang Zonghan Sun Yujia Cao Hengliang Shi Xuejiao Liu Qiong Shi Xiuping Zhou Rutong Yu
author_facet	Shangfeng Gao Lei Jin Guangping Liu Peng Wang Zonghan Sun Yujia Cao Hengliang Shi Xuejiao Liu Qiong Shi Xiuping Zhou Rutong Yu
author_sort	Shangfeng Gao
title	Overexpression of RASD1 inhibits glioma cell migration/invasion and inactivates the AKT/mTOR signaling pathway
title_short	Overexpression of RASD1 inhibits glioma cell migration/invasion and inactivates the AKT/mTOR signaling pathway
title_full	Overexpression of RASD1 inhibits glioma cell migration/invasion and inactivates the AKT/mTOR signaling pathway
title_fullStr	Overexpression of RASD1 inhibits glioma cell migration/invasion and inactivates the AKT/mTOR signaling pathway
title_full_unstemmed	Overexpression of RASD1 inhibits glioma cell migration/invasion and inactivates the AKT/mTOR signaling pathway
title_sort	overexpression of rasd1 inhibits glioma cell migration/invasion and inactivates the akt/mtor signaling pathway
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/686553a62acc4c4abcac280a47e034f8
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Overexpression of RASD1 inhibits glioma cell migration/invasion and inactivates the AKT/mTOR signaling pathway

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