PMID- 35326683
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230102
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 14
IP  - 6
DP  - 2022 Mar 16
TI  - NRF2 and Key Transcriptional Targets in Melanoma Redox Manipulation.
LID - 10.3390/cancers14061531 [doi]
LID - 1531
AB  - Melanocytes are dendritic, pigment-producing cells located in the skin and are 
      responsible for its protection against the deleterious effects of solar 
      ultraviolet radiation (UVR), which include DNA damage and elevated reactive 
      oxygen species (ROS). They do so by synthesizing photoprotective melanin pigments 
      and distributing them to adjacent skin cells (e.g., keratinocytes). However, 
      melanocytes encounter a large burden of oxidative stress during this process, due 
      to both exogenous and endogenous sources. Therefore, melanocytes employ numerous 
      antioxidant defenses to protect themselves; these are largely regulated by the 
      master stress response transcription factor, nuclear factor erythroid 2-related 
      factor 2 (NRF2). Key effector transcriptional targets of NRF2 include the 
      components of the glutathione and thioredoxin antioxidant systems. Despite these 
      defenses, melanocyte DNA often is subject to mutations that result in the 
      dysregulation of the proliferative mitogen-activated protein kinase (MAPK) 
      pathway and the cell cycle. Following tumor initiation, endogenous antioxidant 
      systems are co-opted, a consequence of elevated oxidative stress caused by 
      metabolic reprogramming, to establish an altered redox homeostasis. This altered 
      redox homeostasis contributes to tumor progression and metastasis, while also 
      complicating the application of exogenous antioxidant treatments. Further 
      understanding of melanocyte redox homeostasis, in the presence or absence of 
      disease, would contribute to the development of novel therapies to aid in the 
      prevention and treatment of melanomas and other skin diseases.
FAU - Carpenter, Evan L
AU  - Carpenter EL
AUID- ORCID: 0000-0003-1147-6381
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State 
      University, Corvallis, OR 97331, USA.
FAU - Becker, Alyssa L
AU  - Becker AL
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State 
      University, Corvallis, OR 97331, USA.
AD  - John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA.
FAU - Indra, Arup K
AU  - Indra AK
AUID- ORCID: 0000-0001-6137-7555
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State 
      University, Corvallis, OR 97331, USA.
AD  - Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, 
      USA.
AD  - Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 
      97331, USA.
AD  - Linus Pauling Science Center, Oregon State University, Corvallis, OR 97331, USA.
AD  - Department of Dermatology, Oregon Health & Science University, Portland, OR 
      97239, USA.
LA  - eng
GR  - T32 AT010131/AT/NCCIH NIH HHS/United States
GR  - T32AT010131/AT/NCCIH NIH HHS/United States
GR  - 1R01ES016629-01A1/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20220316
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8946769
OTO - NOTNLM
OT  - HO-1
OT  - HSP70
OT  - NQO1
OT  - NRF2
OT  - SOD
OT  - antioxidant
OT  - glutathione
OT  - melanoma
OT  - peroxiredoxin
OT  - thioredoxin
COIS- The authors state no conflicts of interest.
EDAT- 2022/03/26 06:00
MHDA- 2022/03/26 06:01
PMCR- 2022/03/16
CRDT- 2022/03/25 01:02
PHST- 2022/02/18 00:00 [received]
PHST- 2022/03/13 00:00 [revised]
PHST- 2022/03/14 00:00 [accepted]
PHST- 2022/03/25 01:02 [entrez]
PHST- 2022/03/26 06:00 [pubmed]
PHST- 2022/03/26 06:01 [medline]
PHST- 2022/03/16 00:00 [pmc-release]
AID - cancers14061531 [pii]
AID - cancers-14-01531 [pii]
AID - 10.3390/cancers14061531 [doi]
PST - epublish
SO  - Cancers (Basel). 2022 Mar 16;14(6):1531. doi: 10.3390/cancers14061531.