Moon Eui Jung, Giaccia Amato
Division of Radiation Biology & Oncology, Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.
Division of Radiation Biology & Oncology, Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.
Free Radic Biol Med. 2015 Feb;79:292-9. doi: 10.1016/j.freeradbiomed.2014.11.009. Epub 2014 Nov 29.
The cap'n'collar (CNC) family serves as cellular sensors of oxidative and electrophilic stresses and shares structural similarities including basic leucine zipper (bZIP) and CNC domains. They form heterodimers with small MAF proteins to regulate antioxidant and phase II enzymes through antioxidant response element (ARE)-mediated transactivation. Among the CNC family members, NRF2 is required for systemic protection against redox-mediated injury and carcinogenesis. On the other hand, NRF2 is activated by oncogenic pathways, metabolism, and hypoxia. Constitutive NRF2 activation is observed in a variety of human cancers and it is highly correlated with tumor progression and aggressiveness. In this review, we will discuss how NRF2 plays dual roles in cancer prevention and progression depending on the cellular context and environment. Therefore, a better understanding of NRF2 will be necessary to exploit this complex network of balancing antioxidant pathways to inhibit tumor progression.
帽领（CNC）家族作为细胞对氧化应激和亲电应激的传感器，具有包括碱性亮氨酸拉链（bZIP）和CNC结构域在内的结构相似性。它们与小MAF蛋白形成异二聚体，通过抗氧化反应元件（ARE）介导的反式激活来调节抗氧化酶和II期酶。在CNC家族成员中，NRF2是全身抵抗氧化还原介导的损伤和致癌作用所必需的。另一方面，NRF2可被致癌途径、代谢和缺氧激活。在多种人类癌症中均观察到NRF2的组成性激活，并且它与肿瘤进展和侵袭性高度相关。在本综述中，我们将讨论NRF2如何根据细胞背景和环境在癌症预防和进展中发挥双重作用。因此，有必要更好地了解NRF2，以利用这个复杂的平衡抗氧化途径网络来抑制肿瘤进展。
