DRR1 promotes glioblastoma cell invasion and epithelial-mesenchymal transition via regulating AKT activation. (1st June 2018)

• Record Type: Journal Article
• Authors: Ma, Yu-Shui; Wu, Zhi-Jun; Bai, Rui-Zhen; Dong, Hua; Xie, Bing-Xue; Wu, Xiao-Hong; Hang, Xiao-Sheng; Liu, Ai-Ning; Jiang, Xiao-Hui; Wang, Gao-Ren; Jiang, Jun-Jian; Xu, Wen-Huan; Chen, Xiao-Ping; Tan, Guang-Hong; Fu, Da; Liu, Ji-Bin; Liu, Quan
• Is Part Of: Cancer letters. Volume 423(2018)
• Page Start: 86
• Page End: 94
• Publication Date: 2018-06-01
• Subjects: DRR1 -- EMT -- AKT -- GBM -- Invasion; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2018.03.015
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Metastatic invasion is the primary cause of treatment failure for GBM. EMT is one of the most important events in the invasion of GBM; therefore, understanding the molecular mechanisms of EMT is crucial for the treatment of GBM. In this study, high expression of DRR1 was identified to correlate with a shorter median overall and relapse-free survival. Loss-of-function assays using shDRR1 weakened the invasive potential of the GBM cell lines through regulation of EMT-markers. The expressions of p -AKT were significantly decreased after DRR-depletion in SHG44 and U373 cells. Moreover, the invasion was inhibited by the AKT inhibitor, MK-2206. The expression of Vimentin, N-cadherin, MMP-7, snail and slug was significantly inhibited by MK-2206, while the expression of E-cadherin was upregulated. Our results provide the first evidence that DRR1 is involved in GBM invasion and progression possibly through the induction of EMT activation by phosphorylation of AKT. Graphical abstract: Highlights: DRR1 is involved in GBM invasion and progression. DRR1 promotes EMT by activating AKT. DRR1 may be a prognostic predictor of GBM.