期刊
MOLECULAR CARCINOGENESIS
卷 56, 期 10, 页码 2290-2300出版社
WILEY
DOI: 10.1002/mc.22684
关键词
oxidative stress; PLC-1; skin cell transformation; UCP2
资金
- National Cancer Institute [R21CA164218]
Uncoupling protein 2 (UCP2), whose physiological role is to decrease mitochondrial membrane potential and reactive oxygen species (ROS) production, is often overexpressed in human cancers. UCP2 upregulation has recently been proposed as a novel survival mechanism for cancer cells. However, until now, how exactly UCP2 promotes tumorigenesis remains inconclusive. Based on a widely used skin cell transformation model, our data demonstrated that UCP2 differentially regulated ROS. UCP2 upregulation decreased superoxide whereas it increased hydrogen peroxide production with concomitant increase in the expression and activity of manganese superoxide dismutase (MnSOD), the primary mitochondrial antioxidant enzyme. Furthermore, hydrogen peroxide was responsible for induction of lipid peroxidation, and PLC-1 activation in UCP2 overexpressed cells. Additionally, PLC-1 activation enhanced skin cell transformation, and pharmacological, and siRNA mediated inhibition of PLC-1, markedly reduced colony formation, and 3D cell growth. Moreover, hydrogen peroxide scavenger, catalase, suppressed lipid peroxidation, and dampened PLC-1 activity. Taken together, our data suggest that (i) UCP2 is an important regulator of mitochondrial redox status and lipid signaling; (ii) hydrogen peroxide might mediate UCP2's tumor promoting activity; and (iii) pharmacological disruption of PLC-1 and/or hydrogen peroxide may have clinical utility for UCP2 overexpressed cancers.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据