NRF2在肿瘤预防和进展中的双重作用：对癌症治疗的潜在影响。
Dual roles of NRF2 in tumor prevention and progression: possible implications in cancer treatment.
作者信息
Moon Eui Jung, Giaccia Amato
机构信息
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.
出版信息
Free Radic Biol Med. 2015 Feb;79:292-9. doi: 10.1016/j.freeradbiomed.2014.11.009. Epub 2014 Nov 29.
Abstract
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.
摘要
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。
相似文献
1
Dual roles of NRF2 in tumor prevention and progression: possible implications in cancer treatment.NRF2在肿瘤预防和进展中的双重作用：对癌症治疗的潜在影响。
Free Radic Biol Med. 2015 Feb;79:292-9. doi: 10.1016/j.freeradbiomed.2014.11.009. Epub 2014 Nov 29.
2
Nrf2 defends the lung from oxidative stress.Nrf2保护肺部免受氧化应激的影响。
Antioxid Redox Signal. 2006 Jan-Feb;8(1-2):76-87. doi: 10.1089/ars.2006.8.76.
3
Cancer chemoprevention mechanisms mediated through the Keap1-Nrf2 pathway.癌症化学预防机制通过 Keap1-Nrf2 通路介导。
Antioxid Redox Signal. 2010 Dec 1;13(11):1713-48. doi: 10.1089/ars.2010.3221. Epub 2010 Aug 14.
4
Emerging role of Nrf2 in protecting against hepatic and gastrointestinal disease.Nrf2在预防肝脏和胃肠道疾病中的新作用。
Toxicol Pathol. 2007 Jun;35(4):459-73. doi: 10.1080/01926230701311344.
5
6
Dual roles of Nrf2 in cancer.Nrf2在癌症中的双重作用。
Pharmacol Res. 2008 Nov-Dec;58(5-6):262-70. doi: 10.1016/j.phrs.2008.09.003. Epub 2008 Sep 13.
7
A novel small molecule, N-(4-(2-pyridyl)(1,3-thiazol-2-yl))-2-(2,4,6-trimethylphenoxy) acetamide, selectively protects against oxidative stress-induced cell death by activating the Nrf2-ARE pathway: therapeutic implications for ALS.一种新型小分子 N-(4-(2-吡啶基)(1,3-噻唑-2-基))-2-(2,4,6-三甲基苯氧基)乙酰胺，通过激活 Nrf2-ARE 通路选择性地保护细胞免受氧化应激诱导的细胞死亡：肌萎缩侧索硬化症的治疗意义。
Free Radic Biol Med. 2012 Dec 1;53(11):2028-42. doi: 10.1016/j.freeradbiomed.2012.09.010. Epub 2012 Sep 20.
8
Novel insights into the regulation of antioxidant-response-element-mediated gene expression by electrophiles: induction of the transcriptional repressor BACH1 by Nrf2.电活性物质对抗氧化反应元件介导的基因表达调控的新认识：Nrf2 诱导转录抑制因子 BACH1。
Biochem J. 2011 Dec 1;440(2):167-74. doi: 10.1042/BJ20110526.
9
Natural dietary anti-cancer chemopreventive compounds: redox-mediated differential signaling mechanisms in cytoprotection of normal cells versus cytotoxicity in tumor cells.天然膳食抗癌化学预防化合物：氧化还原介导的正常细胞细胞保护与肿瘤细胞细胞毒性的差异信号传导机制。
Acta Pharmacol Sin. 2007 Apr;28(4):459-72. doi: 10.1111/j.1745-7254.2007.00549.x.
10
The Cap'n'Collar basic leucine zipper transcription factor Nrf2 (NF-E2 p45-related factor 2) controls both constitutive and inducible expression of intestinal detoxification and glutathione biosynthetic enzymes.帽领碱性亮氨酸拉链转录因子Nrf2（NF-E2 p45相关因子2）控制肠道解毒和谷胱甘肽生物合成酶的组成型和诱导型表达。
Cancer Res. 2001 Apr 15;61(8):3299-307.
引用本文的文献
1
Modulating nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in liver-brain axis disorders.调节肝脑轴疾病中的核因子红细胞2相关因子2和血红素加氧酶-1
World J Psychiatry. 2025 Sep 19;15(9):108382. doi: 10.5498/wjp.v15.i9.108382.
2
Targeting Nrf2 in acute myeloid leukemia: an updated review on its role in chemoresistance and emerging therapeutic strategies.靶向急性髓系白血病中的Nrf2：关于其在化疗耐药中的作用及新兴治疗策略的最新综述
Med Oncol. 2025 Sep 1;42(10):460. doi: 10.1007/s12032-025-03012-9.
3
Anticancer potential of eugenol in hepatocellular carcinoma through modulation of oxidative stress, inflammation, apoptosis, and proliferation mechanisms.丁香酚通过调节氧化应激、炎症、细胞凋亡和增殖机制对肝细胞癌的抗癌潜力。
Discov Oncol. 2025 Jun 12;16(1):1080. doi: 10.1007/s12672-025-02243-6.
4
A three-subtype prognostic classification based on base excision repair and oxidative stress genes in lung adenocarcinoma and its relationship with tumor microenvironment.基于碱基切除修复和氧化应激基因的肺腺癌三亚型预后分类及其与肿瘤微环境的关系
Sci Rep. 2025 May 13;15(1):16647. doi: 10.1038/s41598-025-98088-8.
5
Nrf2 in human cancers: biological significance and therapeutic potential.人类癌症中的Nrf2：生物学意义与治疗潜力
Am J Cancer Res. 2024 Aug 25;14(8):3935-3961. doi: 10.62347/LZVO6743. eCollection 2024.
6
The Effects of ML385 on Head and Neck Squamous Cell Carcinoma: Implications for NRF2 Inhibition as a Therapeutic Strategy.ML385 对头颈部鳞状细胞癌的影响：作为一种治疗策略的 NRF2 抑制作用。
Int J Mol Sci. 2024 Jun 27;25(13):7011. doi: 10.3390/ijms25137011.
7
Oxidative stress in hair follicle development and hair growth: Signalling pathways, intervening mechanisms and potential of natural antioxidants.氧化应激在毛囊发育和头发生长中的作用：信号通路、干预机制和天然抗氧化剂的潜力。
J Cell Mol Med. 2024 Jun;28(12):e18486. doi: 10.1111/jcmm.18486.
8
Antioxidant Metabolism Pathways in Vitamins, Polyphenols, and Selenium: Parallels and Divergences.抗氧化剂代谢途径在维生素、多酚和硒中：平行与分歧。
Int J Mol Sci. 2024 Feb 23;25(5):2600. doi: 10.3390/ijms25052600.
9
Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to Immunotherapy.未折叠蛋白反应在治疗抵抗中的新兴机制：从化疗到免疫治疗。
Cell Commun Signal. 2024 Jan 31;22(1):89. doi: 10.1186/s12964-023-01438-0.
10
Exploring the multifaceted role of NRF2 in brain physiology and cancer: A comprehensive review.探索NRF2在脑生理学和癌症中的多方面作用：一篇综述
Neurooncol Adv. 2023 Dec 23;6(1):vdad160. doi: 10.1093/noajnl/vdad160. eCollection 2024 Jan-Dec.
本文引用的文献
1
Structure of the BTB domain of Keap1 and its interaction with the triterpenoid antagonist CDDO.Keap1的BTB结构域及其与三萜类拮抗剂CDDO的相互作用
PLoS One. 2014 Jun 4;9(6):e98896. doi: 10.1371/journal.pone.0098896. eCollection 2014.
2
The Nrf2 transcription factor contributes to resistance to cisplatin in bladder cancer.Nrf2转录因子有助于膀胱癌对顺铂产生耐药性。
Urol Oncol. 2014 Aug;32(6):806-14. doi: 10.1016/j.urolonc.2014.02.006. Epub 2014 May 16.
3
Transcriptomic characterization of hepatocellular carcinoma with CTNNB1 mutation.CTNNB1 突变型肝细胞癌的转录组特征。
PLoS One. 2014 May 5;9(5):e95307. doi: 10.1371/journal.pone.0095307. eCollection 2014.
4
Oncogenic KRAS signalling in pancreatic cancer.胰腺癌中的致癌 KRAS 信号。
Br J Cancer. 2014 Aug 26;111(5):817-22. doi: 10.1038/bjc.2014.215. Epub 2014 Apr 22.
5
Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo.木樨草素抑制体内 Nrf2 信号通路和肿瘤生长。
Biochem Biophys Res Commun. 2014 May 16;447(4):602-8. doi: 10.1016/j.bbrc.2014.04.039. Epub 2014 Apr 18.
6
Correlation of Nrf2, NQO1, MRP1, cmyc and p53 in colorectal cancer and their relationships to clinicopathologic features and survival.Nrf2、NQO1、MRP1、cmyc和p53在结直肠癌中的相关性及其与临床病理特征和生存的关系
Int J Clin Exp Pathol. 2014 Feb 15;7(3):1124-31. eCollection 2014.
7
Nrf2 is useful for predicting the effect of chemoradiation therapy on esophageal squamous cell carcinoma.Nrf2有助于预测放化疗对食管鳞状细胞癌的疗效。
Ann Surg Oncol. 2014 Jul;21(7):2347-52. doi: 10.1245/s10434-014-3600-2. Epub 2014 Mar 6.
8
Clinical significance of Keap1 and Nrf2 in oral squamous cell carcinoma.Keap1 和 Nrf2 在口腔鳞状细胞癌中的临床意义。
PLoS One. 2013 Dec 27;8(12):e83479. doi: 10.1371/journal.pone.0083479. eCollection 2013.
9
Dimethyl fumarate (Tecfidera): a new oral agent for multiple sclerosis.富马酸二甲酯（泰立沙）：一种用于治疗多发性硬化症的新型口服药物。
Ann Pharmacother. 2013 Dec;47(12):1697-702. doi: 10.1177/1060028013509232. Epub 2013 Oct 23.
10
Nrf2 activation supports cell survival during hypoxia and hypoxia/reoxygenation in cardiomyoblasts; the roles of reactive oxygen and nitrogen species.Nrf2激活在心肌母细胞缺氧及缺氧/复氧过程中支持细胞存活；活性氧和氮物种的作用。
Redox Biol. 2013 Aug 22;1(1):418-26. doi: 10.1016/j.redox.2013.08.002. eCollection 2013.
Zotero 插件