Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
BMC Mol Cell Biol. 2023 Feb 6;24(1):5. doi: 10.1186/s12860-023-00466-5.
Melanoma is the most lethal type of skin cancer that originates from the malignant transformation of melanocytes. Although novel treatments have improved patient survival in melanoma, the overall prognosis remains poor. To improve current therapies and patients outcome, it is necessary to identify the influential elements in the development and progression of melanoma.Due to UV exposure and melanin synthesis, the melanocytic lineage seems to have a higher rate of ROS (reactive oxygen species) formation. Melanoma has been linked to an increased oxidative state, and all facets of melanoma pathophysiology rely on redox biology. Several redox-modulating pathways have arisen to resist oxidative stress. One of which, the Nrf2 (nuclear factor erythroid 2-related factor 2), has been recognized as a master regulator of cellular response to oxidative or electrophilic challenges. The activation of Nrf2 signaling causes a wide range of antioxidant and detoxification enzyme genes to be expressed. As a result, this transcription factor has lately received a lot of interest as a possible cancer treatment target.On the other hand, Nrf2 has been found to have a variety of activities in addition to its antioxidant abilities, constant Nrf2 activation in malignant cells may accelerate metastasis and chemoresistance. Hence, based on the cell type and context, Nrf2 has different roles in either preventing or promoting cancer. In this study, we aimed to systematically review all the studies discussing the function of Nrf2 in melanoma and the factors determining its alteration.
黑素瘤是最致命的皮肤癌类型，起源于黑素细胞的恶性转化。尽管新的治疗方法改善了黑素瘤患者的生存，但总体预后仍然不佳。为了改进当前的治疗方法和患者的预后，有必要确定黑素瘤发生和发展过程中的影响因素。由于紫外线暴露和黑色素合成，黑素细胞系似乎具有更高的 ROS（活性氧）形成率。黑素瘤与氧化状态增加有关，黑素瘤病理生理学的各个方面都依赖于氧化还原生物学。已经出现了几种调节氧化还原状态的途径来抵抗氧化应激。其中，Nrf2（核因子红细胞 2 相关因子 2）已被认为是细胞对氧化或亲电应激反应的主要调节剂。Nrf2 信号的激活导致广泛的抗氧化和解毒酶基因的表达。因此，这种转录因子最近作为一种可能的癌症治疗靶点受到了广泛关注。另一方面，除了抗氧化能力外，Nrf2 还具有多种活性，恶性细胞中持续的 Nrf2 激活可能会加速转移和化疗耐药性。因此，基于细胞类型和背景，Nrf2 在预防或促进癌症方面具有不同的作用。在这项研究中，我们旨在系统地回顾所有讨论 Nrf2 在黑素瘤中的功能以及决定其改变的因素的研究。
