NRF2 and Key Transcriptional Targets in Melanoma Redox Manipulation.
NRF2 and Key Transcriptional Targets in Melanoma Redox Manipulation.
复制标题
DOI：
10.3390/cancers14061531
复制
发表时间：
2022-03-16
期刊：
影响因子：
5.2
通讯作者：
Indra AK
中科院分区：
文献类型：
--
作者：
Carpenter EL;Becker AL;Indra AK
黑素细胞是皮肤中的色素产生细胞，有助于保护皮肤免受太阳紫外线辐射的伤害。当它们参与这一功能时，它们会受到过量的氧化应激。为了保护自己，它们利用许多抗氧化系统来减少细胞中存在的活性氧和氮的数量，这种活性有助于预防癌症的形成。然而，在黑色素瘤形成后，这些相同的抗氧化系统通常被癌症吸收，以促进其不受控制的生长和转移。这篇综述的目的是强调黑素细胞的抗氧化系统，由转录因子NRF 2及其靶点调节，在黑色素瘤中是如何被选择的，因此，可以作为治疗黑色素瘤的新疗法的目标。黑素细胞是位于皮肤中的树突状色素产生细胞，并且负责保护其免受太阳紫外线辐射（UVR）的有害影响，包括DNA损伤和升高的活性氧（ROS）。它们通过合成光保护性黑色素并将其分布到相邻的皮肤细胞（例如，角质形成细胞）。然而，由于外源性和内源性来源，黑素细胞在此过程中遇到大量的氧化应激负担。因此，黑素细胞采用许多抗氧化防御来保护自己;这些主要是由主应激反应转录因子，核因子红细胞2相关因子2（NRF 2）调节。NRF 2的关键效应子转录靶标包括谷胱甘肽和硫氧还蛋白抗氧化系统的组分。尽管有这些防御措施，黑素细胞DNA经常发生突变，导致增殖性丝裂原活化蛋白激酶（MAPK）途径和细胞周期失调。肿瘤发生后，内源性抗氧化系统被吸收，这是代谢重编程引起的氧化应激升高的结果，以建立改变的氧化还原稳态。这种改变的氧化还原稳态有助于肿瘤进展和转移，同时也使外源性抗氧化剂治疗的应用复杂化。进一步了解黑素细胞的氧化还原稳态，在存在或不存在疾病的情况下，将有助于开发新的疗法，以帮助预防和治疗黑色素瘤和其他皮肤病
Melanocytes are the pigment-producing cells in the skin that help to protect it against damaging solar ultraviolet radiation. As they engage in this function, they are subject to an inordinate amount of oxidative stress. To protect themselves, they utilize numerous antioxidant systems to reduce the amount of reactive oxygen and nitrogen species present in the cells, and this activity then contributes towards the prevention of cancer formation. However, after the formation of melanomas these same antioxidant systems are often co-opted by the cancer in order to promote its uncontrolled growth and metastasis. The purpose of this review is to highlight how the melanocyte’s antioxidant systems, regulated by the transcription factor NRF2 and its targets, are co-opted in melanomas and, therefore, could be targeted for novel therapies to treat melanomas going forward. Melanocytes are dendritic, pigment-producing cells located in the skin and are responsible for its protection against the deleterious effects of solar ultraviolet radiation (UVR), which include DNA damage and elevated reactive oxygen species (ROS). They do so by synthesizing photoprotective melanin pigments and distributing them to adjacent skin cells (e.g., keratinocytes). However, melanocytes encounter a large burden of oxidative stress during this process, due to both exogenous and endogenous sources. Therefore, melanocytes employ numerous antioxidant defenses to protect themselves; these are largely regulated by the master stress response transcription factor, nuclear factor erythroid 2-related factor 2 (NRF2). Key effector transcriptional targets of NRF2 include the components of the glutathione and thioredoxin antioxidant systems. Despite these defenses, melanocyte DNA often is subject to mutations that result in the dysregulation of the proliferative mitogen-activated protein kinase (MAPK) pathway and the cell cycle. Following tumor initiation, endogenous antioxidant systems are co-opted, a consequence of elevated oxidative stress caused by metabolic reprogramming, to establish an altered redox homeostasis. This altered redox homeostasis contributes to tumor progression and metastasis, while also complicating the application of exogenous antioxidant treatments. Further understanding of melanocyte redox homeostasis, in the presence or absence of disease, would contribute to the development of novel therapies to aid in the prevention and treatment of melanomas and other skin diseases
登录
查看更多内容
影响因子：
3.7
作者：
Rotte A;Bhandaru M;Cheng Y;Sjoestroem C;Martinka M;Li G
通讯作者：
Li G
影响因子：
3.5
作者：
Brown, Kristin K.;Cox, Andrew G.;Hampton, Mark B.
通讯作者：
Hampton, Mark B.
影响因子：
4
作者：
Carretero, J;Obrador, E;Estrela, JM
通讯作者：
Estrela, JM
影响因子：
158.5
作者：
Chen, Andrew C.;Martin, Andrew J.;Damian, Diona L.
通讯作者：
Damian, Diona L.
影响因子：
7.4
作者：
Canning P;Sorrell FJ;Bullock AN
通讯作者：
Bullock AN