PMID- 35359389
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230311
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 12
DP  - 2022
TI  - Melanoma, Melanin, and Melanogenesis: The Yin and Yang Relationship.
PG  - 842496
LID - 10.3389/fonc.2022.842496 [doi]
LID - 842496
AB  - 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-1alpha) 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.
CI  - Copyright (c) 2022 Slominski, Sarna, Plonka, Raman, Brozyna and Slominski.
FAU - Slominski, Radomir M
AU  - Slominski RM
AD  - Graduate Biomedical Sciences Program, University of Alabama at Birmingham, 
      Birmingham, AL, United States.
FAU - Sarna, Tadeusz
AU  - Sarna T
AD  - Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, 
      Jagiellonian University, Krakow, Poland.
FAU - Plonka, Przemyslaw M
AU  - Plonka PM
AD  - Department of Biophysics and Cancer Biology, Faculty of Biochemistry, Biophysics 
      and Biotechnology, Jagiellonian University, Krakow, Poland.
FAU - Raman, Chander
AU  - Raman C
AD  - Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, 
      United States.
FAU - Brozyna, Anna A
AU  - Brozyna AA
AD  - Department of Human Biology, Institute of Biology, Faculty of Biological and 
      Veterinary Sciences, Nicolaus Copernicus University, Torun, Poland.
FAU - Slominski, Andrzej T
AU  - Slominski AT
AD  - Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, 
      United States.
AD  - Pathology Laboratory Service, Veteran Administration Medical Center at 
      Birmingham, Birmingham, AL, United States.
LA  - eng
GR  - I01 BX004293/BX/BLRD VA/United States
GR  - R01 AR071189/AR/NIAMS NIH HHS/United States
GR  - R01 AR073004/AR/NIAMS NIH HHS/United States
GR  - R21 AI149267/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20220314
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC8963986
OTO - NOTNLM
OT  - immune responses
OT  - melanin
OT  - melanocytes
OT  - melanogenesis
OT  - melanoma
OT  - melanoma progression
OT  - melanoma therapy
OT  - oxidative stress
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/02 06:00
MHDA- 2022/04/02 06:01
PMCR- 2022/01/01
CRDT- 2022/04/01 05:09
PHST- 2021/12/23 00:00 [received]
PHST- 2022/01/24 00:00 [accepted]
PHST- 2022/04/01 05:09 [entrez]
PHST- 2022/04/02 06:00 [pubmed]
PHST- 2022/04/02 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2022.842496 [doi]
PST - epublish
SO  - Front Oncol. 2022 Mar 14;12:842496. doi: 10.3389/fonc.2022.842496. eCollection 
      2022.