Dual roles of NRF2 in tumor prevention and progression: possible implications in cancer treatment.

Dual roles of NRF2 in tumor prevention and progression: possible implications in cancer treatment.
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DOI:
10.1016/j.freeradbiomed.2014.11.009
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发表时间:
2015-02
影响因子:
7.4
通讯作者:
Giaccia, Amato
Giaccia, Amato
中科院分区:
医学1区
文献类型:
--
作者:
Moon, Eui Jung;Giaccia, Amato

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Cap'N'Collar(CNC)家族作为氧化和亲电应激的细胞传感器,并且共享结构相似性,包括碱性亮氨酸拉链(bZIP)和CNC结构域。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相酶。在CNC家族成员中,NRF2是针对氧化还原介导的损伤和致癌作用的全身保护所必需的。另一方面,NRF2被致癌途径、代谢和缺氧激活。在多种人类癌症中观察到组成性NRF2活化,并且其与肿瘤进展和侵袭性高度相关。在这篇综述中,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,更好地了解NRF2将是必要的,以利用这种复杂的网络平衡抗氧化剂途径,以抑制肿瘤的进展。
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.
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