DRR1 通过调节 AKT 的激活促进胶质母细胞瘤细胞的侵袭和上皮-间充质转化。
DRR1 promotes glioblastoma cell invasion and epithelial-mesenchymal transition via regulating AKT activation.
机构信息
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, College of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
Department of Radiotherapy, Nantong Tumor Hospital, Nantong 226631, China.
出版信息
Cancer Lett. 2018 Jun 1;423:86-94. doi: 10.1016/j.canlet.2018.03.015. Epub 2018 Mar 13.
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.
转移浸润是 GBM 治疗失败的主要原因。上皮间质转化（EMT）是 GBM 浸润的最重要事件之一；因此，了解 EMT 的分子机制对于 GBM 的治疗至关重要。在这项研究中，高表达 DRR1 与较短的中位总生存期和无复发生存期相关。使用 shDRR1 的功能丧失测定削弱了通过 EMT 标志物调节的 GBM 细胞系的侵袭潜力。在 SHG44 和 U373 细胞中 DRR 耗竭后，p-AKT 的表达明显降低。此外，AKT 抑制剂 MK-2206 抑制了侵袭。MK-2206 显著抑制波形蛋白、N-钙粘蛋白、MMP-7、snail 和 slug 的表达，而上皮钙粘蛋白的表达上调。我们的研究结果首次提供证据表明，DRR1 可能通过 AKT 磷酸化诱导 EMT 激活而参与 GBM 的浸润和进展。
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