Laboratory for Immunology of Skin Diseases, Chair and Department of Dermatology, Venerology and Paediatric Dermatology, Medical University of Lublin, Radziwillowska 11, 20-080 Lublin, Poland.
Chair and Department of Dermatology, Venerology and Paediatric Dermatology, Medical University of Lublin, Staszica 11Ł, 20-081 Lublin, Poland
Int J Mol Sci. 2023 Feb 4;24(4):3114. doi: 10.3390/ijms24043114.
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors involved in various physiological and pathological processes within the skin. PPARs regulate several processes in one of the most aggressive skin cancers, melanoma, including proliferation, cell cycle, metabolic homeostasis, cell death, and metastasis. In this review, we focused not only on the biological activity of PPAR isoforms in melanoma initiation, progression, and metastasis but also on potential biological interactions between the PPAR signaling and the kynurenine pathways. The kynurenine pathway is a major pathway of tryptophan metabolism leading to nicotinamide adenine dinucleotide (NAD+) production. Importantly, various tryptophan metabolites exert biological activity toward cancer cells, including melanoma. Previous studies confirmed the functional relationship between PPAR and the kynurenine pathway in skeletal muscles. Despite the fact this interaction has not been reported in melanoma to date, some bioinformatics data and biological activity of PPAR ligands and tryptophan metabolites may suggest a potential involvement of these metabolic and signaling pathways in melanoma initiation, progression, and metastasis. Importantly, the possible relationship between the PPAR signaling pathway and the kynurenine pathway may relate not only to the direct biological effect on melanoma cells but also to the tumor microenvironment and the immune system.
过氧化物酶体增殖物激活受体 (PPARs) 是配体激活的转录因子，参与皮肤内的各种生理和病理过程。PPARs 调节黑色素瘤中包括增殖、细胞周期、代谢稳态、细胞死亡和转移在内的多种过程。在这篇综述中，我们不仅关注了 PPAR 亚型在黑色素瘤起始、进展和转移中的生物学活性，还关注了 PPAR 信号与犬尿氨酸途径之间潜在的生物学相互作用。犬尿氨酸途径是色氨酸代谢的主要途径，导致烟酰胺腺嘌呤二核苷酸 (NAD+) 的产生。重要的是，各种色氨酸代谢物对癌细胞（包括黑色素瘤）具有生物学活性。先前的研究证实了 PPAR 和骨骼肌中犬尿氨酸途径之间的功能关系。尽管迄今为止尚未在黑色素瘤中报道这种相互作用，但一些生物信息学数据和 PPAR 配体和色氨酸代谢物的生物学活性可能表明这些代谢和信号通路可能参与黑色素瘤的起始、进展和转移。重要的是，PPAR 信号通路和犬尿氨酸途径之间的可能关系不仅与对黑色素瘤细胞的直接生物学效应有关，还与肿瘤微环境和免疫系统有关。
