Furfaro A L, Traverso N, Domenicotti C, Piras S, Moretta L, Marinari U M, Pronzato M A, Nitti M
Giannina Gaslini Institute, Via Gerolamo Gaslini 5, 16147 Genoa, Italy.
Department of Experimental Medicine, University of Genoa, Via L. B. Alberti 2, 16132 Genoa, Italy.
Oxid Med Cell Longev. 2016;2016:1958174. doi: 10.1155/2016/1958174. Epub 2015 Nov 30.
The transcription factor, nuclear factor erythroid 2 p45-related factor 2 (Nrf2), acts as a sensor of oxidative or electrophilic stresses and plays a pivotal role in redox homeostasis. Oxidative or electrophilic agents cause a conformational change in the Nrf2 inhibitory protein Keap1 inducing the nuclear translocation of the transcription factor which, through its binding to the antioxidant/electrophilic response element (ARE/EpRE), regulates the expression of antioxidant and detoxifying genes such as heme oxygenase 1 (HO-1). Nrf2 and HO-1 are frequently upregulated in different types of tumours and correlate with tumour progression, aggressiveness, resistance to therapy, and poor prognosis. This review focuses on the Nrf2/HO-1 stress response mechanism as a promising target for anticancer treatment which is able to overcome resistance to therapies.
转录因子核因子红细胞2相关因子2（Nrf2）作为氧化应激或亲电应激的感受器，在氧化还原稳态中起关键作用。氧化或亲电试剂会导致Nrf2抑制蛋白Keap1发生构象变化，从而诱导转录因子的核转位，该转录因子通过与抗氧化/亲电反应元件（ARE/EpRE）结合，调节抗氧化和解毒基因如血红素加氧酶1（HO-1）的表达。Nrf2和HO-1在不同类型肿瘤中常被上调，并与肿瘤进展、侵袭性、治疗耐药性及预后不良相关。本综述聚焦于Nrf2/HO-1应激反应机制，将其作为一种有望克服治疗耐药性的抗癌治疗靶点。
