UVA, metabolism and melanoma: UVA makes melanoma hungry for metastasis

Abstract

Ultraviolet (UV) radiation has a plethora of effects on human tissues. In the UV spectrum, wavelengths above 320 nm fall into the UVA range, and for these, it has been shown that they induce reactive oxygen species (ROS), DNA mutations and are capable to induce melanoma in mice. In addition to this, it was recently shown that UVA irradiation and UVA-induced ROS also increase glucose metabolism of melanoma cells. UVA irradiation causes a persistent increase in glucose consumption, accompanied by increased glycolysis, increased lactic acid production and activation of the pentose phosphate pathway. Furthermore, it was shown that the enhanced secretion of lactic acid is important for invasion of melanoma in vitro. The current knowledge of this link between UVA, metabolism and melanoma, possible mechanisms of UVA-induced glucose metabolism and their starting points are discussed in this review with focus on ROS- and UVA-induced cellular stress signalling, DNA damage signalling and DNA repair systems. When looking at the benefits of UVA-induced glucose metabolism, it becomes apparent that there are more advantages of these metabolic changes than one would expect. Besides the role of lactic acid as initiator of protease expression and invasion, its role for immune escape of melanoma cells and the pentose phosphate pathway-derived nicotinamide adenine dinucleotide phosphate (NADPH) as part of a ROS detoxification strategy are discussed.

Oxidative Stress and Genotoxicity in Melanoma Induction: Impact on Repair Rather Than Formation of DNA Damage?

“…For instance, its ability to promote cell survival through pathways like PTEN inactivation or to increase proliferation by the ERK pathway is major process in the promotion step. UVA-induced oxidative stress could also be involved in the metastases of melanoma through the induction of metabolic changes (142). Altogether, it appears too restrictive to limit the role of oxidative stress in melanoma to the induction of DNA lesions that could be at the origin of mutations.…”

Comprehensive analysis of cancer hallmarks in cutaneous melanoma and identification of a novel unfolded protein response as a prognostic signature

“…Firstly, we identified 7 hallmarks differentially activated in melanoma, which including UV response up, reactive oxygen species pathway, glycolysis, mTORC1 signal, E2F targets, unfolded protein response and DNA repair. It’s generally accepted that ultraviolet light (UV) considered as the most risk environment factor for initiation of melanoma [ 9 ]. High exposure of UV will upregulate the UV response pathways in cellular signal and then UV induced reactive oxygen species regarded as an important mutagen causes damage of skin cells is also well known [ 25 ].…”

“…Whether there exist different biological signaling regulations between melanoma and nevi is not clear. However, gene mutation result in genetic diversity and susceptibility to DNA damage stimulated by ultraviolet light were the obviously definitive reasons [ 9 ]. Genomic technologies analysis has proved several genetic mutations and correlated pathways are closely associated with melanoma initiation and progression [ 10 , 11 ].…”

A Review of Exogenous Factors Implicated in the Induction of Cutaneous Melanoma

“…9 UVA is thought to induce cutaneous melanoma indirectly through reactive oxygen species (ROS) and immunosuppression. [21][22][23] In particular, it has been proposed that melanin acts as the key photosensitizer in the pathogenesis of cutaneous melanoma via ROS. 18 UVA's role in the pathogenesis of cutaneous melanoma appears infrequently contested in modern literature.…”