Ablation of TAK1 upregulates reactive oxygen species and selectively kills tumor cells.
Ablation of TAK1 upregulates reactive oxygen species and selectively kills tumor cells.
复制标题
DOI：
10.1158/0008-5472.can-10-1227
复制
发表时间：
2010-11-01
期刊：
影响因子：
11.2
通讯作者：
Ninomiya-Tsuji J
中科院分区：
文献类型：
--
作者：
Omori E;Matsumoto K;Zhu S;Smart RC;Ninomiya-Tsuji J
TAK1激酶激活多种转录因子，调节活性氧（ROS）水平。我们之前报道过，角质形成细胞中TAK1的消融会导致ros诱导的细胞凋亡的超敏感性。众所周知，一些肿瘤细胞比正常细胞产生更高水平的活性氧。我们利用可诱导的表皮特异性TAK1基因敲除小鼠，研究了在皮肤肿瘤前切除TAK1是否会导致ROS增加并导致肿瘤细胞死亡。皮肤肿瘤中tak1基因的缺失导致ROS的积累和细胞凋亡的增加，皮肤肿瘤在5-10天内完全消退。tak1基因缺失后，正常皮肤未出现明显异常。因此，TAK1激酶可能是ros杀伤肿瘤的一个新的、有效的分子靶点。
TAK1 kinase activates multiple transcription factors and regulates the level of reactive oxygen species (ROS). We have previously reported that ablation of TAK1 in keratinocytes causes hyper-sensitivity to ROS-induced cell apoptosis. It is known that some tumor cells produce ROS at higher levels compared to normal cells. We utilized inducible epidermal specific TAK1 knockout mice, and examined whether ablation of TAK1 in pre-exiting skin tumors could cause an increase in ROS and result in tumor cell death. Deletion of tak1 gene in skin tumors caused the accumulation of ROS and increased apoptosis, and skin tumors totally regressed within 5-10 days. Normal skin did not exhibit any significant abnormality upon tak1 gene deletion. Thus, TAK1 kinase could be a new and effective molecular target for ROS-based tumor killing.