PMID- 33215847
OWN - NLM
STAT- MEDLINE
DCOM- 20211227
LR  - 20211227
IS  - 1755-148X (Electronic)
IS  - 1755-1471 (Linking)
VI  - 34
IP  - 2
DP  - 2021 Mar
TI  - The unfolded protein and integrated stress response in melanoma and vitiligo.
PG  - 204-211
LID - 10.1111/pcmr.12947 [doi]
AB  - Epidermal melanocytes are constantly exposed to environmental stressors such as 
      ultraviolet light (UV) and chemotoxins. Several evolutionarily conversed survival 
      mechanisms are deployed to ensure melanocyte recovery after damage including the 
      unfolded protein response (UPR) and integrated stress response (ISR). The UPR/ISR 
      promote restoration of homeostasis, by modulating transcription and translation 
      as well as activating nuclear factor erythroid 2-related factor 2 (NRF2)-mediated 
      antioxidant activity. If repair fails, the UPR/ISR either stimulate cell death, 
      or adaptation that can lead to survival of damaged cells and promote disease. For 
      example, the UPR/ISR may support melanomagenesis by allowing UV-damaged, mutated 
      cells to survive and adapt to a hostile tumor microenvironment that subjects 
      cells to hypoxia, nutrient deprivation, and sub-optimal pH. The UPR and ISR can 
      also promote transcriptional changes that support tumor growth and/or metastasis. 
      Furthermore, these pathways may also underlie acquisition of chemoresistance and 
      modulation of protein expression that alters the efficacy of immunotherapies. UPR 
      activation has also been implicated in the pathogenesis of vitiligo and may 
      promote increased expression of chemokines such as interleukin 6 and interleukin 
      8 that trigger an autoimmune response against melanocytes. We herein review the 
      potential roles of the UPR/ISR in the etiology of melanoma and vitiligo.
CI  - (c) 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Manga, Prashiela
AU  - Manga P
AUID- ORCID: 0000-0001-5501-0343
AD  - Ronald O. Perelman Department of Dermatology, New York University Grossman School 
      of Medicine, New York, NY, USA.
FAU - Choudhury, Noshin
AU  - Choudhury N
AUID- ORCID: 0000-0002-5841-1684
AD  - Ronald O. Perelman Department of Dermatology, New York University Grossman School 
      of Medicine, New York, NY, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20201202
PL  - England
TA  - Pigment Cell Melanoma Res
JT  - Pigment cell & melanoma research
JID - 101318927
SB  - IM
MH  - Animals
MH  - Humans
MH  - Melanoma/etiology/metabolism/*pathology
MH  - *Stress, Physiological
MH  - *Unfolded Protein Response
MH  - Vitiligo/etiology/metabolism/*pathology
OTO - NOTNLM
OT  - integrated stress response
OT  - melanocyte damage
OT  - melanoma
OT  - unfolded protein response
OT  - vitiligo
EDAT- 2020/11/21 06:00
MHDA- 2021/12/28 06:00
CRDT- 2020/11/20 08:41
PHST- 2020/09/05 00:00 [received]
PHST- 2020/10/28 00:00 [revised]
PHST- 2020/11/17 00:00 [accepted]
PHST- 2020/11/21 06:00 [pubmed]
PHST- 2021/12/28 06:00 [medline]
PHST- 2020/11/20 08:41 [entrez]
AID - 10.1111/pcmr.12947 [doi]
PST - ppublish
SO  - Pigment Cell Melanoma Res. 2021 Mar;34(2):204-211. doi: 10.1111/pcmr.12947. Epub 
      2020 Dec 2.