Department of Pathology, Paul F. Glenn Laboratories for Aging, Harvard Medical School, Boston, MA, USA.
Cancer Res. 2012 May 15;72(10):2468-72. doi: 10.1158/0008-5472.CAN-11-3633.
Tumors exhibit metabolic reprogramming characterized by increased cellular reactive oxygen species (ROS) and the preferential use of glucose, which is known as the Warburg effect. However, the mechanisms by which these processes are linked remain largely elusive. Murine tumors lacking Sirt3 exhibit abnormally high levels of ROS that directly induce genomic instability and increase hypoxia-inducible factor 1α (HIF-1α) protein levels. The subsequent transcription of HIFα-dependent target genes results in cellular metabolic reprogramming and increased cellular glucose consumption. In addition, agents that scavenge ROS or reverse the Warburg effect prevent the transformation and malignant phenotype observed in cells lacking Sirt3. Thus, mice lacking Sirt3 provide a model that mechanistically connects aberrant ROS, the Warburg effect, and carcinogenesis.
肿瘤表现出代谢重编程的特征，其特征为细胞内活性氧（ROS）增加和优先使用葡萄糖，这被称为沃伯格效应。然而，这些过程是如何联系起来的机制在很大程度上仍然难以捉摸。缺乏 Sirt3 的鼠肿瘤表现出异常高水平的 ROS，这些 ROS 直接诱导基因组不稳定性并增加缺氧诱导因子 1α（HIF-1α）蛋白水平。随后，HIFα 依赖性靶基因的转录导致细胞代谢重编程和细胞葡萄糖消耗增加。此外，清除 ROS 或逆转沃伯格效应的试剂可防止观察到的缺乏 Sirt3 的细胞中的转化和恶性表型。因此，缺乏 Sirt3 的小鼠提供了一个机制上连接异常 ROS、沃伯格效应和致癌作用的模型。
