PPARs and the Kynurenine Pathway in Melanoma-Potential Biological Interactions

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.

Automated summary

Peroxisome proliferator-activated receptors (PPARs) are involved in various processes in the skin, including melanoma, and there may be potential interactions between the PPAR signaling pathway and the kynurenine pathway. The kynurenine pathway is a major pathway of tryptophan metabolism and produces metabolites that have biological activity in cancer cells. Although the relationship between PPAR and the kynurenine pathway has not been reported in melanoma, there are indications of potential involvement in melanoma initiation, progression, and metastasis. The PPAR signaling pathway may also have effects on the tumor microenvironment and immune system.