Wu Jianing, Liu Yaohua, Cho KenKa, Dong Xingli, Teng Lei, Han Dayong, Liu Huailei, Chen Xiaofeng, Chen Xin, Hou Xu, Peng Fei, Bi Yunke, Shen Chen, Zhao Shiguang
aDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University bBrain Science Institute of Harbin Medical University cDepartment of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, People's Republic of China dDepartment of Acupuncture, Takarazuka University of Medical and Health Care, Takarazuka City, Japan.
Neuroreport. 2016 Feb 10;27(3):136-44. doi: 10.1097/WNR.0000000000000513.
Cancer cells preferentially use aerobic glycolysis to support growth, a metabolic alteration commonly referred to as the 'Warburg effect.' Here, we show that the tumor necrosis factor receptor-associated protein 1 (TRAP1) is crucial for the Warburg effect in human glioblastoma multiforme (GBM). In contrast to normal brain, GBMs show increased TRAP1 expression. We used both GBM cell lines and neurospheres derived from human GBM specimens to examine the effects of Knockdown of TRAP1 on GBM cell lines and glioma stem cells. We also used a neurosphere recovery assay that measured neurosphere formation at three time points to assess the capacity of the culture to repopulate after knockdown of TRAP1. Our results showed that knockdown of TRAP1 strongly decreased GBM cell proliferation and migration, inhibited neurosphere recovery, secondary neurosphere formation, and enhanced the therapeutic effect of temozolomide in neurosphere cultures. In GBM, knockdown of TRAP1 appeared to inhibit tumor growth and migration through its regulatory effects on metabolic reprogramming.
癌细胞优先利用有氧糖酵解来支持生长，这种代谢改变通常被称为“瓦伯格效应”。在此，我们表明肿瘤坏死因子受体相关蛋白1（TRAP1）对于多形性胶质母细胞瘤（GBM）中的瓦伯格效应至关重要。与正常脑组织相比，GBM中TRAP1表达增加。我们使用GBM细胞系和源自人类GBM标本的神经球来研究敲低TRAP1对GBM细胞系和胶质瘤干细胞的影响。我们还使用了一种神经球恢复试验，该试验在三个时间点测量神经球形成，以评估敲低TRAP1后培养物重新增殖的能力。我们的结果表明，敲低TRAP1可强烈降低GBM细胞增殖和迁移，抑制神经球恢复、次级神经球形成，并增强替莫唑胺在神经球培养物中的治疗效果。在GBM中，敲低TRAP1似乎通过其对代谢重编程的调节作用来抑制肿瘤生长和迁移。
