High SLC7A11 expression in normal skin of melanoma patients
High SLC7A11 expression in normal skin of melanoma patients
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DOI：
10.1016/j.canep.2019.101582
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发表时间：
2019-10-01
影响因子：
2.6
通讯作者：
Bernabeu-Wittel, Jose
中科院分区：
文献类型：
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作者：
Galvan, Ismael;Inacio, Angela;Bernabeu-Wittel, Jose
背景：黑色素瘤是转移性最高的癌症之一，其发病率正在迅速增加。目前，研究人员致力于黑色素瘤细胞基因突变和表达谱的研究，但对黑色素细胞中黑色素合成对黑色素瘤发生的可能影响的研究较少。SLC 7A 11编码胱氨酸/谷氨酸反向转运蛋白xCT，其表达通过提供可用于谷胱甘肽（GSH）合成的半胱氨酸来增加细胞的抗氧化能力。然而，黑素细胞也可以使用半胱氨酸来合成褐黑素和色素沉着。因此，褐黑素的合成可能导致慢性氧化应激。可能的后果，这为melanomagenesis从来没有explored.Methods：我们量化的SLC 7A 11和其他基因的表达，参与合成的褐黑素，但不调节半胱氨酸的运输从细胞外介质的胞质溶胶（CTNS，MC 1 R，ASIP和SLC 45 A2）在非肿瘤皮肤的45例皮肤黑色素瘤患者和50名健康人。我们控制了菲茨帕特里克皮肤类型、年龄、性别、体重、日晒和晒伤频率、黑色素细胞痣数量以及由基因NFE 2L 2表达所提供的内在抗氧化能力的影响。结果：SLC 7A 11的表达在黑色素瘤患者中显著高于健康个体，而其他基因的表达则不显著。这是独立的表型因素和抗氧化能力，从而支持的影响，褐黑素诱导的氧化应激对melanomagenesis.Conclusion：我们的研究结果表明，SLC 7A 11下调正常表皮黑素细胞可能代表一种预防性治疗黑色素瘤。
Background: Melanoma is one of the highest metastatic cancers and its incidence is rapidly increasing. A great effort has been devoted to determine gene mutations and expression profiles in melanoma cells, but less attention has been given to the possible influence of melanin synthesis in melanocytes on melanomagenesis. SLC7A11 encodes the cystine/glutamate antiporter xCT and its expression increases the antioxidant capacity of cells by providing cysteine that may be used for glutathione (GSH) synthesis. Melanocytes, however, can also use cysteine for pheomelanin synthesis and pigmentation. Therefore, pheomelanin synthesis may lead to chronic oxidative stress. Possible consequences of this for melanomagenesis have never been explored.Methods: We quantified the expression of SLC7A11 and other genes that are involved in the synthesis of pheomelanin but do not regulate the transport of cysteine from the extracellular medium to the cytosol (CTNS, MC1R, ASIP and SLC45A2) in non-tumorous skin of 45 patients of cutaneous melanoma and 50 healthy individuals. We controlled for the effects of Fitzpatrick skin type, age, gender, body mass, frequency of sun exposure and sunburns and number of melanocytic nevi, as well as for the intrinsic antioxidant capacity as given by the expression of the gene NFE2L2.Results: The expression of SLC7A11, but not of the other genes, was significantly higher in melanoma patients than in healthy individuals. This was independent of phenotypic factors and antioxidant capacity, thus supporting an effect of pheomelanin-induced oxidative stress on melanomagenesis.Conclusion: Our findings indicate that SLC7A11 downregulation in normal epidermal melanocytes may represent a preventive treatment against melanoma.