Xu Ke, Pei Hua, Zhang Zhenhao, Dong Sufang, Fu Rui-Jia, Wang Wen-Ming, Wang Huamin
Department of Immunology, School of Tropical and Laboratory Medicine, Hainan Medical University, Haikou, Hainan 571101, P.R. China.
Medical Technology Institute of Xuzhou Medical College, Xuzhou, Jiangsu 221004, P.R. China.
Oncol Rep. 2016 Nov;36(5):3044-3050. doi: 10.3892/or.2016.5087. Epub 2016 Sep 12.
The role of FoxO3a in glioma progression is poorly defined. Herein, we show that silencing FoxO3a in U251 cells leads to decreased invasive migration and proliferation, while ectopic expression of FoxO3a in U87 cells with weak endogenous FoxO3a protein levels enhances invasion and proliferation. To further investigate the mechanism by which FoxO3a promotes invasion, we detected key members of the matrix metalloproteinases (MMPs) that are associated with invasion. Our findings showed that, among these MMP members, only FoxO3a induced MMP9 expression, and MMP9 overexpression reversed the effect that silencing FoxO3a had on the attenuation of cell invasion. Taken together, these data link FoxO3a to the promotion of metastasis in glioma cells.
FoxO3a在胶质瘤进展中的作用尚不明确。在此，我们表明，沉默U251细胞中的FoxO3a会导致侵袭性迁移和增殖减少，而在具有弱内源性FoxO3a蛋白水平的U87细胞中异位表达FoxO3a会增强侵袭和增殖。为了进一步研究FoxO3a促进侵袭的机制，我们检测了与侵袭相关的基质金属蛋白酶（MMPs）的关键成员。我们的研究结果表明，在这些MMP成员中，只有FoxO3a诱导MMP9表达，并且MMP9过表达逆转了沉默FoxO3a对细胞侵袭减弱的影响。综上所述，这些数据将FoxO3a与胶质瘤细胞转移的促进联系起来。
