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Review
. 2024 Oct 30;25(21):11651.
doi: 10.3390/ijms252111651.

Current Insights into the Role of UV Radiation-Induced Oxidative Stress in Melanoma Pathogenesis

Ernest Gieniusz  1 , Elżbieta Skrzydlewska  1 , Wojciech Łuczaj  1
Affiliations
Review

Current Insights into the Role of UV Radiation-Induced Oxidative Stress in Melanoma Pathogenesis

Ernest Gieniusz et al. Int J Mol Sci. .

Abstract

Cutaneous melanoma accounts for the majority of skin cancer-related deaths, and its incidence increases each year. The growing number of melanoma cases, especially in advanced stages, poses a significant socio-medical challenge throughout the world. Extensive research on melanoma pathogenesis identifies UV radiation as the most important factor in melanocytic transformation. Oxidative effects of UV irradiation exert their influence on melanoma pathogenesis primarily through modification of nucleic acids, proteins, and lipids, further disrupting cellular signaling and cell cycle regulation. Its effects extend beyond melanocytes, leading to immunosuppression in the exposed skin tissue, which consequently creates conditions for immune surveillance evasion and further progression. In this review, we focus on the specific molecular changes observed in the UV-dependent oxidative stress environment and their biological consequences in the course of the disease, which have not been considered in previous reviews on melanoma. Nonetheless, data show that the exact role of oxidative stress in melanoma initiation and progression remains unclear, as it affects cancerous cells differently depending on the specific context. A better understanding of the pathophysiological basis of melanoma development holds promise for identifying potential targets, which could lead to effective melanoma prevention strategies.

Keywords: UV radiation; cellular signaling; melanocytes; melanoma; melanoma metastasis; melanoma progression; molecular background; oxidative stress.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The most important molecular signaling pathways activated by UV irradiation and their involvement in the pathogenesis of melanoma [34,35,36,37,40,41,42,43,44]. AKT—protein kinase B; Bcl-2—B-cell lymphoma 2; BRAF—v-Raf murine sarcoma viral oncogene homolog B; cAMP—cyclic adenosine monophosphate; CDKN2A—cyclin-dependent kinase inhibitor 2A; CDKs—cyclin-dependent kinases; c-KIT—tyrosine-protein kinase KIT; c-MET—mesenchymal-epithelial transition factor; DAG—diacylglycerol; ERK—extracellular signal-regulated kinase; GF—growth factors; GPCR—G protein-coupled receptors; HIF—hypoxia-inducible factor; IGF-1—insulin-like growth factor 1; IKK—inhibitor of nuclear factor-κB (IκB) kinase; MAPK—mitogen-activated protein kinases; MC1R—melanocortin 1 receptor; MEK—mitogen-activated protein kinase; MITF—microphthalmia-associated transcription factor; mTOR—mammalian target of rapamycin; NF-1—neurofibromin 1; Nf-kB—nuclear factor kappa-light-chain enhancer of activated B cells; Notch—neurogenic locus notch homolog proteins; PI3K—phosphatidylinositol 3-kinase; PIP3—phosphatidylinositol 3-phosphate; PKC—protein kinase C; PLC—phospholipase C; PTEN—phosphatase and tensin homolog; RAS—“rat sarcoma virus” protein family; RTK—receptor tyrosine kinases; SCF—stem cell factor; SOX10—Sry-related HMg-Box gene 10; TNFR1—tumor necrosis factor receptor 1; WNT—“wingless-related integration site” protein family. Created with BioRender.com.
Figure 2
Figure 2
Mechanisms of the formation of UV-induced mutagenic lesions in melanocytes. ROS—reactive oxygen species, CPD—cyclobutane pyrimidine dimers, NER—nucleotide excision repair, T—thymine, A—adenine. Created with BioRender.com.
Figure 3
Figure 3
The effects of UV radiation leading to development of melanoma. FB—fibroblast. Created with BioRender.com.
Figure 4
Figure 4
Differences in redox status over the course of melanomagenesis. CHO—carbohydrates, DOPAQ—dopachinone, FMN—flavin mononucleotide, HIF-1—hypoxia-induced factor 1, Tyr—tyrosine. Created with BioRender.com.
Figure 5
Figure 5
The impact of oxidative stress on melanomagenesis. TF—transcription factor. Created with BioRender.com.
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Grants and funding

The publication of this paper was supported by the Ministry of Science and Education in Poland.

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