• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell discovery. >The ERK signaling target RNF126 regulates anoikis resistance in cancer cells by changing the mitochondrial metabolic flux
【24h】

The ERK signaling target RNF126 regulates anoikis resistance in cancer cells by changing the mitochondrial metabolic flux

机译：ERK信号转导靶标RNF126通过改变线粒体代谢通量来调节癌细胞的无源抗药性

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Loss of anchorage to the extracellular matrix leads to apoptosis (anoikis) in normal cells, but cancerous cells are usually resistant to such stress. Here we report the pivotal role of an E3 ubiquitin ligase, ring-finger protein 126 (RNF126), in the resistance of cancer cells to the stress associated with non-adherent conditions. Non-adherent cancer cells exhibited increased flux through the tricarboxylic acid cycle via increased conversion of pyruvate to acetyl-CoA. RNF126 was found to act as a ubiquitin ligase for pyruvate dehydrogenase kinases (PDKs), resulting in their proteasomal degradation. This decrease in PDK levels allowed pyruvate dehydrogenases to catalyze the conversion of pyruvate to acetyl-CoA. Moreover, depletion of RNF126 or increased expression of PDK1 in cancer cells suppressed colony formation in soft agar as well as tumorigenicity in mice. RNF126 expression in cancer cells was found to be under the control of the extracellular signal-regulated kinase signaling pathway, which is essential for anoikis resistance. Thus, RNF126 is an attractive molecule for treating cancer by selectively targeting anchorage-independent growth.
机译：丧失对细胞外基质的锚定会导致正常细胞凋亡（凋亡），但是癌细胞通常对这种压力具有抵抗力。在这里，我们报告了E3泛素连接酶，环指蛋白126（RNF126）在癌细胞对与非粘附性疾病相关的应激的抵抗中的关键作用。非粘附癌细胞通过丙酮酸向乙酰辅酶A的转化增加，表现出通过三羧酸循环的通量增加。发现RNF126充当丙酮酸脱氢酶激酶（PDK）的泛素连接酶，导致其蛋白酶体降解。 PDK水平的这种降低使丙酮酸脱氢酶能够催化丙酮酸向乙酰辅酶A的转化。此外，癌细胞中RNF126的减少或PDK1的表达增加抑制了软琼脂中的菌落形成以及小鼠的致瘤性。发现癌细胞中的RNF126表达受细胞外信号调节的激酶信号传导途径的控制，这对于失代偿抗性是必不可少的。因此，RNF126是通过选择性靶向锚定非依赖性生长来治疗癌症的有吸引力的分子。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号