AEG-1 promotes mesenchymal transition through the activation of Rho GTPases in human glioblastoma cells

Park,Sang-Yoon; Choi,Minji; Park,Dain; Jeong,Minho; Ahn,Kwang Seok; Lee,Junhee; Fisher,Paul B.; Yun,Miyong; Lee,Seok-Geun

doi:10.3892/or.2016.5106

AEG-1 promotes mesenchymal transition through the activation of Rho GTPases in human glioblastoma cells

Authors:
- Sang-Yoon Park
- Minji Choi
- Dain Park
- Minho Jeong
- Kwang Seok Ahn
- Junhee Lee
- Paul B. Fisher
- Miyong Yun
- Seok-Geun Lee
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Affiliations: Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea, Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital, Seoul 02447, Republic of Korea, Department of Cancer Preventive Material Development, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea, Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, VCU Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA
Published online on: September 19, 2016 https://doi.org/10.3892/or.2016.5106
Pages: 2641-2646

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Abstract

Despite growing evidence indicating that astrocyte elevated gene-1 (AEG-1) plays pivotal roles in tumor progression in various types of human cancers including brain tumors; to date, its role in the regulation of mesenchymal transition is not clear in glioblastoma. In the present study, we investigated the contribution of AEG-1 to stress fiber formation and then the acquisition of mesenchymal characteristics of glioblastoma cells. Gain- and loss-of-function studies in normal immortalized primary human fetal astrocytes (IM-PHFAs) and glioblastoma cells revealed that overexpression of AEG-1 increased expression of mesenchymal markers including N-cadherin and two mesenchymal transition‑inducing transcription factors ZEB1 and Slug but decreased epithelial markers E-cadherin and ZO-1. In addition, knockdown of AEG-1 suppressed invasive ability and migration of glioblastoma cells. Overexpression of AEG-1 also induced stress fiber formation and activated the Rho GTPase signaling pathways in glioblastoma cells. Consistently, treatment with an RhoA inhibitor decreased AEG-1-mediated stress fiber formation in glioblastoma cells. Collectively, our findings suggest that AEG-1 promotes mesenchymal transition in glioblastoma through the regulation of the Rho signaling pathway, resulting in tumor invasion, a primary characteristic of malignant brain tumors.

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