PMID- 36830722
OWN - NLM
STAT- MEDLINE
DCOM- 20230228
LR  - 20230310
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 13
IP  - 2
DP  - 2023 Feb 11
TI  - Reactive Oxygen Species and NRF2 Signaling, Friends or Foes in Cancer?
LID - 10.3390/biom13020353 [doi]
LID - 353
AB  - The imbalance between reactive oxygen species (ROS) production and clearance 
      causes oxidative stress and ROS, which play a central role in regulating cell and 
      tissue physiology and pathology. Contingent upon concentration, ROS influence 
      cancer development in contradictory ways, either stimulating cancer survival and 
      growth or causing cell death. Cells developed evolutionarily conserved programs 
      to sense and adapt redox the fluctuations to regulate ROS as either signaling 
      molecules or toxic insults. The transcription factor nuclear factor erythroid 
      2-related factor 2 (NRF2)-KEAP1 system is the master regulator of cellular redox 
      and metabolic homeostasis. NRF2 has Janus-like roles in carcinogenesis and cancer 
      development. Short-term NRF2 activation suppresses tissue injury, inflammation, 
      and cancer initiation. However, cancer cells often exhibit constitutive NRF2 
      activation due to genetic mutations or oncogenic signaling, conferring advantages 
      for cancer cells' survival and growth. Emerging evidence suggests that NRF2 
      hyperactivation, as an adaptive cancer phenotype under stressful tumor 
      environments, regulates all hallmarks of cancer. In this review, we summarized 
      the source of ROS, regulation of ROS signaling, and cellular sensors for ROS and 
      oxygen (O(2)), we reviewed recent progress on the regulation of ROS generation 
      and NRF2 signaling with a focus on the new functions of NRF2 in cancer 
      development that reach beyond what we originally envisioned, including regulation 
      of cancer metabolism, autophagy, macropinocytosis, unfolded protein response, 
      proteostasis, and circadian rhythm, which, together with anti-oxidant and drug 
      detoxification enzymes, contributes to cancer development, metastasis, and 
      anticancer therapy resistance.
FAU - Wang, Ruolei
AU  - Wang R
AD  - The Center for Cancer Research, Academy of Integrative Medicine, Shanghai 
      University of Traditional Chinese Medicine, Shanghai 201203, China.
FAU - Liang, Lirong
AU  - Liang L
AD  - Department of Respiratory and Critical Care Medicine, Beijing Institute of 
      Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, 
      Beijing 100020, China.
FAU - Matsumoto, Misaki
AU  - Matsumoto M
AD  - Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto 
      602-8566, Japan.
FAU - Iwata, Kazumi
AU  - Iwata K
AUID- ORCID: 0000-0002-9595-7782
AD  - Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto 
      602-8566, Japan.
FAU - Umemura, Atsushi
AU  - Umemura A
AD  - Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto 
      602-8566, Japan.
FAU - He, Feng
AU  - He F
AUID- ORCID: 0000-0003-0276-3303
AD  - The Center for Cancer Research, Academy of Integrative Medicine, Shanghai 
      University of Traditional Chinese Medicine, Shanghai 201203, China.
LA  - eng
GR  - 82172947/National Natural Science Foundation of China/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20230211
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - Humans
MH  - Reactive Oxygen Species/metabolism
MH  - Kelch-Like ECH-Associated Protein 1/metabolism
MH  - *NF-E2-Related Factor 2/metabolism
MH  - *Neoplasms/metabolism
MH  - Oxidative Stress
PMC - PMC9953152
OTO - NOTNLM
OT  - NRF2
OT  - ROS
OT  - inflammation
OT  - metabolism
OT  - oxidative stress
OT  - unfolded protein response
COIS- The authors declare that the research was conducted without any commercial or 
      financial relationships that could be construed as a potential conflict of 
      interest.
EDAT- 2023/02/26 06:00
MHDA- 2023/03/03 06:00
PMCR- 2023/02/11
CRDT- 2023/02/25 01:23
PHST- 2022/12/06 00:00 [received]
PHST- 2023/02/03 00:00 [revised]
PHST- 2023/02/09 00:00 [accepted]
PHST- 2023/02/25 01:23 [entrez]
PHST- 2023/02/26 06:00 [pubmed]
PHST- 2023/03/03 06:00 [medline]
PHST- 2023/02/11 00:00 [pmc-release]
AID - biom13020353 [pii]
AID - biomolecules-13-00353 [pii]
AID - 10.3390/biom13020353 [doi]
PST - epublish
SO  - Biomolecules. 2023 Feb 11;13(2):353. doi: 10.3390/biom13020353.