The emerging role of the Nrf2-Keap1 signaling pathway in cancer.
The emerging role of the Nrf2-Keap1 signaling pathway in cancer.
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DOI：
10.1101/gad.225680.113
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发表时间：
2013-10-15
影响因子：
10.5
通讯作者：
Zhang DD
中科院分区：
文献类型：
--
作者：
Jaramillo MC;Zhang DD
Nrf 2-Keap 1信号通路是细胞防御和存活途径的关键。Nrf 2可以保护细胞和组织免受有毒物质和致癌物质的侵害，目前正在测试几种Nrf 2激活剂作为化学预防化合物。然而，一些研究也表明，Nrf 2可以保护癌细胞免受化疗药物的影响，并促进癌细胞增殖。在这里，Jaramillo和Zhang提供了癌症中Nrf 2-Keap 1信号通路的概述。他们讨论了Nrf 2在癌症中的双重作用以及开发基于Nrf 2的化学预防和治疗药物的挑战。Nrf 2（nuclear factor erythroid 2 [NF-E2]-related factor 2 [Nrf 2]）-Keap 1（Kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1）信号通路是最重要的细胞防御和存活通路之一。nrf 2可以通过增加许多细胞保护基因的表达来保护细胞和组织免受各种毒物和致癌物的侵害。因此，几种Nrf 2激活剂目前正在临床试验中作为化学预防化合物进行测试。正如Nrf 2保护正常细胞一样，研究表明Nrf 2也可以保护癌细胞免受化疗药物的影响，并促进癌症进展。nrf 2在许多类型的癌症中异常积累，并且其表达与患者的不良预后相关。此外，Nrf 2表达在耐药性过程中被诱导。总的来说，这些研究表明，Nrf 2有助于内在和获得性耐药性。这一发现开辟了一个广泛的研究领域，旨在更好地了解Nrf 2在癌症中的作用。本文综述了（1）Nrf 2-Keap 1信号通路，（2）Nrf 2在癌症中的双重作用，（3）Nrf 2在癌细胞中活化的分子基础，以及（4）基于Nrf 2的化学预防和化疗药物开发中的挑战。
The Nrf2–Keap1 signaling pathway is key to cell defense and survival pathways. Nrf2 can protect cells and tissues from toxicants and carcinogens, and several Nrf2 activators are currently being tested as chemopreventive compounds. However, several studies also suggest that Nrf2 may protect cancer cells from chemotherapeutic agents and promote cancer cell proliferation. Here, Jaramillo and Zhang provide an overview of the Nrf2–Keap1 signaling pathway in cancer. They discuss the dual role of Nrf2 in cancer and the challenges in developing Nrf2-based drugs for chemoprevention and therapy. The Nrf2 (nuclear factor erythroid 2 [NF-E2]-related factor 2 [Nrf2])–Keap1 (Kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1) signaling pathway is one of the most important cell defense and survival pathways. Nrf2 can protect cells and tissues from a variety of toxicants and carcinogens by increasing the expression of a number of cytoprotective genes. As a result, several Nrf2 activators are currently being tested as chemopreventive compounds in clinical trials. Just as Nrf2 protects normal cells, studies have shown that Nrf2 may also protect cancer cells from chemotherapeutic agents and facilitate cancer progression. Nrf2 is aberrantly accumulated in many types of cancer, and its expression is associated with a poor prognosis in patients. In addition, Nrf2 expression is induced during the course of drug resistance. Collectively, these studies suggest that Nrf2 contributes to both intrinsic and acquired chemoresistance. This discovery has opened up a broad spectrum of research geared toward a better understanding of the role of Nrf2 in cancer. This review provides an overview of (1) the Nrf2–Keap1 signaling pathway, (2) the dual role of Nrf2 in cancer, (3) the molecular basis of Nrf2 activation in cancer cells, and (4) the challenges in the development of Nrf2-based drugs for chemoprevention and chemotherapy.
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DOI：
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发表时间：
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期刊：
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影响因子：
--
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