PMID- 30760522
OWN - NLM
STAT- MEDLINE
DCOM- 20191213
LR  - 20231006
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 79
IP  - 5
DP  - 2019 Mar 1
TI  - NRF2 Activation in Cancer: From DNA to Protein.
PG  - 889-898
LID - 10.1158/0008-5472.CAN-18-2723 [doi]
AB  - The Cancer Genome Atlas catalogued alterations in the Kelch-like ECH-associated 
      protein 1 and nuclear factor erythroid 2-related factor 2 (NRF2) signaling 
      pathway in 6.3% of patient samples across 226 studies, with significant 
      enrichment in lung and upper airway cancers. These alterations constitutively 
      activate NRF2-dependent gene transcription to promote many of the cancer 
      hallmarks, including cellular resistance to oxidative stress, xenobiotic efflux, 
      proliferation, and metabolic reprogramming. Almost universally, NRF2 activity 
      strongly associates with poor patient prognosis and chemo- and radioresistance. 
      Yet to date, FDA-approved drugs targeting NRF2 activity in cancer have not been 
      realized. Here, we review various mechanisms that contribute to NRF2 activation 
      in cancer, organized around the central dogma of molecular biology (i) at the DNA 
      level with genomic and epigenetic alterations, (ii) at the RNA level including 
      differential mRNA splicing and stability, and (iii) at the protein level 
      comprising altered posttranslational modifications and protein-protein 
      interactions. Ultimately, defining and understanding the mechanisms responsible 
      for NRF2 activation in cancer may lead to novel targets for therapeutic 
      intervention.
CI  - (c)2019 American Association for Cancer Research.
FAU - Cloer, Erica W
AU  - Cloer EW
AD  - Department of Cell Biology and Physiology, University of North Carolina at Chapel 
      Hill School of Medicine, Chapel Hill, North Carolina.
AD  - Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel 
      Hill School of Medicine, Chapel Hill, North Carolina.
FAU - Goldfarb, Dennis
AU  - Goldfarb D
AUID- ORCID: 0000-0002-1584-5423
AD  - Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel 
      Hill School of Medicine, Chapel Hill, North Carolina.
AD  - Department of Computer Science, University of North Carolina at Chapel Hill, 
      Chapel Hill, North Carolina.
FAU - Schrank, Travis P
AU  - Schrank TP
AD  - Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel 
      Hill School of Medicine, Chapel Hill, North Carolina.
AD  - Department of Otolaryngology/Head and Neck Surgery, University of North Carolina 
      at Chapel Hill School of Medicine, Chapel Hill, North Carolina.
FAU - Weissman, Bernard E
AU  - Weissman BE
AD  - Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel 
      Hill School of Medicine, Chapel Hill, North Carolina.
AD  - Department of Pathology and Laboratory Medicine, University of North Carolina at 
      Chapel Hill School of Medicine, Chapel Hill, North Carolina.
FAU - Major, Michael B
AU  - Major MB
AD  - Department of Cell Biology and Physiology, University of North Carolina at Chapel 
      Hill School of Medicine, Chapel Hill, North Carolina. ben_major@med.unc.edu.
AD  - Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel 
      Hill School of Medicine, Chapel Hill, North Carolina.
AD  - Department of Computer Science, University of North Carolina at Chapel Hill, 
      Chapel Hill, North Carolina.
AD  - Department of Pharmacology, University of North Carolina at Chapel Hill School of 
      Medicine, Chapel Hill, North Carolina.
LA  - eng
GR  - R01 CA216051/CA/NCI NIH HHS/United States
GR  - T32 CA009156/CA/NCI NIH HHS/United States
GR  - TL1 TR001110/TR/NCATS NIH HHS/United States
GR  - T32 CA071341/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20190213
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (RNA, Messenger)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - DNA/genetics/*metabolism
MH  - Epigenesis, Genetic
MH  - Humans
MH  - NF-E2-Related Factor 2/genetics/*metabolism
MH  - RNA, Messenger/genetics/metabolism
PMC - PMC6397706
MID - NIHMS1516941
COIS- Disclosure of Potential Conflicts of Interest The authors declare no potential 
      conflicts of interest.
EDAT- 2019/02/15 06:00
MHDA- 2019/12/18 06:00
PMCR- 2020/03/01
CRDT- 2019/02/15 06:00
PHST- 2018/09/13 00:00 [received]
PHST- 2018/11/16 00:00 [revised]
PHST- 2018/12/11 00:00 [accepted]
PHST- 2019/02/15 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/02/15 06:00 [entrez]
PHST- 2020/03/01 00:00 [pmc-release]
AID - 0008-5472.CAN-18-2723 [pii]
AID - 10.1158/0008-5472.CAN-18-2723 [doi]
PST - ppublish
SO  - Cancer Res. 2019 Mar 1;79(5):889-898. doi: 10.1158/0008-5472.CAN-18-2723. Epub 
      2019 Feb 13.