Perspectives of the Nrf-2 signaling pathway in cancer progression and therapy.
Perspectives of the Nrf-2 signaling pathway in cancer progression and therapy.
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DOI：
10.1016/j.toxrep.2017.06.002
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发表时间：
2017
影响因子：
--
通讯作者：
Sil PC
中科院分区：
文献类型：
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作者：
Basak P;Sadhukhan P;Sarkar P;Sil PC
核因子红细胞2相关因子2（Nrf 2）是氧化还原稳态的主要调节因子，是调节抗氧化剂和解毒酶的广泛基因的关键转录因子。它保护器官免受各种有毒物质的侵害。另一方面，Nrf 2的活化也与癌症进展和化学抗性相关。Nrf 2活性的下调已经吸引了越来越多的关注，因为它可以提供替代的癌症治疗。在这篇综述中，我们研究了Nrf 2在几种病理生理条件下的作用，强调癌症的最新研究。我们详细讨论了目前的知识Nrf 2的调控，包括KEAP 1依赖和KEAP 1独立的级联。KEAP 1/Nrf 2系统是细胞对各种环境应激反应的主要调节因子。我们还强调了许多蛋白质，小分子，有毒金属等Nrf 2的几个严格控制的法规。此外，我们评估了可能的治疗方法，通过调节Nrf 2信号增加化疗敏感性。
The Nuclear factor erythroid2-related factor2 (Nrf2), a master regulator of redox homoeostasis, is a key transcription factor regulating a wide array of genes for antioxidant and detoxification enzymes. It protects organs from various kinds of toxic insults. On the other hand, activation of Nrf2 is also correlated with cancer progression and chemoresistance. Downregulation of Nrf2 activity has attracted an increasing amount of attention as it may provide an alternative cancer therapy. In this review, we examine recent studies on roles of Nrf2 in several pathophysiological conditions emphasising cancer. We discuss elaborately the current knowledge on Nrf2 regulation including KEAP1-dependent and KEAP1-independent cascades. KEAP1/Nrf2 system is a master regulator of cellular response against a variety of environmental stresses. We also highlight several tightly controlled regulations of Nrf2 by numerous proteins, small molecules, toxic metals, etc. In addition, we evaluate the possible therapeutic approaches of increasing chemosensitivity via modulating Nrf2 signaling.