PMID- 36994476
OWN - NLM
STAT- MEDLINE
DCOM- 20230331
LR  - 20240204
IS  - 0219-1032 (Electronic)
IS  - 1016-8478 (Print)
IS  - 1016-8478 (Linking)
VI  - 46
IP  - 3
DP  - 2023 Mar 31
TI  - The Multi-Faceted Consequences of NRF2 Activation throughout Carcinogenesis.
PG  - 176-186
LID - 10.14348/molcells.2023.2191 [doi]
AB  - The oxidative balance of a cell is maintained by the Kelch-like ECH-associated 
      protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway. 
      This cytoprotective pathway detoxifies reactive oxygen species and xenobiotics. 
      The role of the KEAP1/NRF2 pathway as pro-tumorigenic or anti-tumorigenic 
      throughout stages of carcinogenesis (including initiation, promotion, 
      progression, and metastasis) is complex. This mini review focuses on key studies 
      describing how the KEAP1/NRF2 pathway affects cancer at different phases. The 
      data compiled suggest that the roles of KEAP1/NRF2 in cancer are highly dependent 
      on context; specifically, the model used (carcinogen-induced vs genetic), the 
      tumor type, and the stage of cancer. Moreover, emerging data suggests that 
      KEAP1/NRF2 is also important for regulating the tumor microenvironment and how 
      its effects are amplified either by epigenetics or in response to co-occurring 
      mutations. Further elucidation of the complexity of this pathway is needed in 
      order to develop novel pharmacological tools and drugs to improve patient 
      outcomes.
FAU - Occhiuto, Christopher J
AU  - Occhiuto CJ
AUID- ORCID: 0000-0002-2218-4504
AD  - Department of Pharmacology and Toxicology, Michigan State University, East 
      Lansing, MI 48824, USA.
AD  - College of Human Medicine, Michigan State University, East Lansing, MI 48824, 
      USA.
FAU - Moerland, Jessica A
AU  - Moerland JA
AUID- ORCID: 0000-0002-8085-3470
AD  - Department of Pharmacology and Toxicology, Michigan State University, East 
      Lansing, MI 48824, USA.
AD  - College of Osteopathic Medicine, Michigan State University, East Lansing, MI 
      48824, USA.
FAU - Leal, Ana S
AU  - Leal AS
AUID- ORCID: 0000-0001-6472-2879
AD  - Department of Pharmacology and Toxicology, Michigan State University, East 
      Lansing, MI 48824, USA.
AD  - College of Osteopathic Medicine, Michigan State University, East Lansing, MI 
      48824, USA.
FAU - Gallo, Kathleen A
AU  - Gallo KA
AUID- ORCID: 0000-0002-9194-3498
AD  - Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
FAU - Liby, Karen T
AU  - Liby KT
AUID- ORCID: 0000-0003-3317-3437
AD  - Department of Pharmacology and Toxicology, Michigan State University, East 
      Lansing, MI 48824, USA.
AD  - College of Osteopathic Medicine, Michigan State University, East Lansing, MI 
      48824, USA.
LA  - eng
GR  - R01 CA226690/CA/NCI NIH HHS/United States
GR  - T32 GM142521/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20230322
PL  - United States
TA  - Mol Cells
JT  - Molecules and cells
JID - 9610936
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
SB  - IM
MH  - Humans
MH  - Carcinogenesis/genetics
MH  - Kelch-Like ECH-Associated Protein 1/genetics/metabolism
MH  - *Neoplasms/genetics/metabolism
MH  - *NF-E2-Related Factor 2/genetics/metabolism
MH  - Signal Transduction
MH  - Tumor Microenvironment
PMC - PMC10070161
OTO - NOTNLM
OT  - NRF2
OT  - cancer
OT  - initiation
OT  - metastasis
OT  - promotion
OT  - transformation
COIS- CONFLICT OF INTEREST K.T.L. is a named inventor on patents issued and filed for 
      synthetic triterpenoids and NRF2 pathway inhibitors. Other authors have no 
      potential conflicts of interest to disclose.
EDAT- 2023/03/31 06:00
MHDA- 2023/03/31 06:41
PMCR- 2023/03/22
CRDT- 2023/03/30 03:06
PHST- 2022/12/16 00:00 [received]
PHST- 2023/02/22 00:00 [revised]
PHST- 2023/02/22 00:00 [accepted]
PHST- 2023/03/31 06:41 [medline]
PHST- 2023/03/30 03:06 [entrez]
PHST- 2023/03/31 06:00 [pubmed]
PHST- 2023/03/22 00:00 [pmc-release]
AID - S1016-8478(23)00023-7 [pii]
AID - molce-46-3-176 [pii]
AID - 10.14348/molcells.2023.2191 [doi]
PST - ppublish
SO  - Mol Cells. 2023 Mar 31;46(3):176-186. doi: 10.14348/molcells.2023.2191. Epub 2023 
      Mar 22.