The ROS-NOX connection in cancer and angiogenesis
The ROS-NOX connection in cancer and angiogenesis
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DOI：
10.1615/critreveukargeneexpr.v18.i1.30
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发表时间：
2008-01-01
影响因子：
1.6
通讯作者：
Boonstra, Johannes
中科院分区：
文献类型：
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作者：
Blanchetot, Christophe;Boonstra, Johannes
活性氧最初被认为是有氧生活的危险副产品，现在似乎是许多信号级联和细胞功能的重要第二信使。ROS作为重要信号分子的确立已经通过在非吞噬细胞中表达的专门的ROS产生复合物（NADPH氧化酶复合物（NOX））的存在来证实。由于其蛋白质靶点的多样性（除了脂质和DNA），ROS具有多种功能，有时相互矛盾。在本综述中，我们集中在几个不同的信号通路的影响ROS和NOX在肿瘤的发生，侧重于增殖和血管生成。我们回顾了ROS调节增殖的靶点，包括细胞信号传导（磷酸酶、AP 1和核因子-κ B [NF-κ B B]）和细胞周期靶点（CDC 25、细胞周期蛋白D和叉头蛋白），以及NOX在增殖过程中的作用。最后，我们回顾了ROS和NOX通过调节不同的生物系统，如血管内皮生长因子，血管紧张素II，缺氧诱导因子，AP 1和炎症，直接和间接参与（肿瘤）血管生成。
Initially viewed as dangerous byproducts of aerobic life, reactive oxygen species (ROS) nowadays appear to be essential secondary messengers of many signaling cascades and cellular functions. The establishment of ROS as important signaling molecules has been confirmed by the existence of specialized ROS producing complexes expressed in nonphagocytic cells, the NADPH oxidase complex (NOX). Because of the diversity of their proteic targets (besides lipids and DNA), ROS have multiple and sometimes contradictory functions. In the present review, we focus on several different signaling pathways influenced by ROS and NOX in tumorigenesis, focusing on proliferation and angiogenesis. We review the ROS targets regulating proliferation, including cellular signaling (phosphatases, AP1, and nuclear factor-kappa B [NF-kappa B]) and cell cycle targets (CDC25, cyclin D, and forkhead proteins), and the role of NOX during proliferation. Finally, we review the direct and indirect involvement of ROS and NOX in (tumor) angiogenesis through the regulation of different biologic systems such as vascular endothelial growth factor, angiotensin II, hypoxia-inducible factor, AP1, and inflammation.