Melanoma, Melanin, and Melanogenesis: The Yin and Yang Relationship.
Melanoma, Melanin, and Melanogenesis: The Yin and Yang Relationship.
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DOI：
10.3389/fonc.2022.842496
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发表时间：
2022
影响因子：
4.7
通讯作者：
Slominski AT
中科院分区：
文献类型：
--
作者：
Slominski RM;Sarna T;Płonka PM;Raman C;Brożyna AA;Slominski AT
黑色素在防止紫外线辐射和其他环境压力的有害影响方面起着关键作用。它是由L-酪氨酸酶促转化为多巴醌，随后的化学和生物化学反应导致形成各种5，6-二羟基吲哚-2-羧酸（DHICA）和5，6-二羟基吲哚（DHI）寡聚体-真黑素的主要成分，以及褐黑素的苯并噻嗪和苯并噻唑单元。黑色素的生物合成受阳光照射和组织、细胞和亚细胞水平上的许多激素因素的调节。虽然黑色素的存在可以防止皮肤癌包括皮肤黑色素瘤的发展，但它的存在可能是黑色素细胞恶性转化所必需的。这表明黑素生成在黑色素瘤发展中的复杂作用，其由黑色素的化学性质和生成途径（例如褐黑素生成）的性质定义。虽然真黑素被认为通过充当有效的抗氧化剂和防晒剂而提供辐射防护和光防护，但褐黑素的光稳定性较低，在暴露于短波长UVR后可产生致突变环境。黑素生成本身及其高活性中间体显示出细胞毒性、遗传毒性和致突变活性，并且它可以刺激糖酵解和缺氧诱导因子1-α（HIF-1α）活化，这与其免疫抑制作用相结合，可以导致黑色素瘤进展和对免疫治疗的抵抗。另一方面，黑素生成相关蛋白可以成为免疫治疗的靶点。有趣的是，对晚期黑色素瘤的临床病理学分析显示，肿瘤色素沉着与疾病结局（由总生存期和无病时间定义）之间呈负相关。这表明黑色素和活性黑色素生成在黑色素瘤发展、进展和治疗中的“阴阳”作用。此外，基于临床，实验数据和黑素生成的不同影响，我们提出，在晚期黑色素性黑色素瘤中抑制黑素生成是一种现实的辅助策略，以增强免疫，放射和化疗。
Melanin pigment plays a critical role in the protection against the harmful effects of ultraviolet radiation and other environmental stressors. It is produced by the enzymatic transformation of L-tyrosine to dopaquinone and subsequent chemical and biochemical reactions resulting in the formation of various 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and 5,6-dihydroxyindole (DHI) oligomers—main constituents of eumelanin, and benzothiazine and benzothiazole units of pheomelanin. The biosynthesis of melanin is regulated by sun exposure and by many hormonal factors at the tissue, cellular, and subcellular levels. While the presence of melanin protects against the development of skin cancers including cutaneous melanoma, its presence may be necessary for the malignant transformation of melanocytes. This shows a complex role of melanogenesis in melanoma development defined by chemical properties of melanin and the nature of generating pathways such as eu- and pheomelanogenesis. While eumelanin is believed to provide radioprotection and photoprotection by acting as an efficient antioxidant and sunscreen, pheomelanin, being less photostable, can generate mutagenic environment after exposure to the short-wavelength UVR. Melanogenesis by itself and its highly reactive intermediates show cytotoxic, genotoxic, and mutagenic activities, and it can stimulate glycolysis and hypoxia-inducible factor 1-alpha (HIF-1α) activation, which, combined with their immunosuppressive effects, can lead to melanoma progression and resistance to immunotherapy. On the other hand, melanogenesis-related proteins can be a target for immunotherapy. Interestingly, clinicopathological analyses on advanced melanomas have shown a negative correlation between tumor pigmentation and diseases outcome as defined by overall survival and disease-free time. This indicates a “Yin and Yang” role for melanin and active melanogenesis in melanoma development, progression, and therapy. Furthermore, based on the clinical, experimental data and diverse effects of melanogenesis, we propose that inhibition of melanogenesis in advanced melanotic melanoma represents a realistic adjuvant strategy to enhance immuno-, radio-, and chemotherapy.
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影响因子：
5.6
作者：
Brożyna AA;Jochymski C;Janjetovic Z;Jóźwicki W;Tuckey RC;Slominski AT
通讯作者：
Slominski AT
影响因子：
1.5
作者：
Brash DE
通讯作者：
Brash DE
影响因子：
3.4
作者：
BRUENGER, FW;STOVER, BJ;ATHERTON, DR
通讯作者：
ATHERTON, DR
DOI：
10.1016/b978-0-12-397927-8.00004-x
发表时间：
2012
期刊：
Advances in pharmacology (San Diego, Calif.)
影响因子：
--
作者：
Bailey, Kate M;Wojtkowiak, Jonathan W;Hashim, Arig Ibrahim;Gillies, Robert J
通讯作者：
Gillies, Robert J
影响因子：
2
作者：
Brozyna, Anna A.;Hoffman, Robert M.;Slominski, Andrzej T.
通讯作者：
Slominski, Andrzej T.