PMID- 38424190
OWN - NLM
STAT- MEDLINE
DCOM- 20240403
LR  - 20240405
IS  - 2092-6413 (Electronic)
IS  - 1226-3613 (Print)
IS  - 1226-3613 (Linking)
VI  - 56
IP  - 3
DP  - 2024 Mar
TI  - Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in 
      cancer.
PG  - 501-514
LID - 10.1038/s12276-024-01180-8 [doi]
AB  - Oxygen is crucial for life and acts as the final electron acceptor in 
      mitochondrial energy production. Cells adapt to varying oxygen levels through 
      intricate response systems. Hypoxia-inducible factors (HIFs), including HIF-1alpha 
      and HIF-2alpha, orchestrate the cellular hypoxic response, activating genes to 
      increase the oxygen supply and reduce expenditure. Under conditions of excess 
      oxygen and resulting oxidative stress, nuclear factor erythroid 2-related factor 
      2 (NRF2) activates hundreds of genes for oxidant removal and adaptive cell 
      survival. Hypoxia and oxidative stress are core hallmarks of solid tumors and 
      activated HIFs and NRF2 play pivotal roles in tumor growth and progression. The 
      complex interplay between hypoxia and oxidative stress within the tumor 
      microenvironment adds another layer of intricacy to the HIF and NRF2 signaling 
      systems. This review aimed to elucidate the dynamic changes and functions of the 
      HIF and NRF2 signaling pathways in response to conditions of hypoxia and 
      oxidative stress, emphasizing their implications within the tumor milieu. 
      Additionally, this review explored the elaborate interplay between HIFs and NRF2, 
      providing insights into the significance of these interactions for the 
      development of novel cancer treatment strategies.
CI  - (c) 2024. The Author(s).
FAU - Bae, Taegeun
AU  - Bae T
AD  - Integrated Research Institute for Pharmaceutical Sciences, The Catholic 
      University of Korea, Bucheon, Gyeonggi‑do, 14662, Republic of Korea.
FAU - Hallis, Steffanus Pranoto
AU  - Hallis SP
AD  - Department of Pharmacy, Graduate School of The Catholic University of Korea, 
      Bucheon, Gyeonggi‑do, 14662, Republic of Korea.
FAU - Kwak, Mi-Kyoung
AU  - Kwak MK
AUID- ORCID: 0000-0001-6254-2516
AD  - Integrated Research Institute for Pharmaceutical Sciences, The Catholic 
      University of Korea, Bucheon, Gyeonggi‑do, 14662, Republic of Korea. 
      mkwak@catholic.ac.kr.
AD  - Department of Pharmacy, Graduate School of The Catholic University of Korea, 
      Bucheon, Gyeonggi‑do, 14662, Republic of Korea. mkwak@catholic.ac.kr.
AD  - College of Pharmacy, The Catholic University of Korea, Bucheon, Gyeonggi‑do, 
      14662, Republic of Korea. mkwak@catholic.ac.kr.
LA  - eng
GR  - 2022R1A2C2011866/National Research Foundation of Korea (NRF)/
GR  - 2018R1A6A1A03025108/National Research Foundation of Korea (NRF)/
PT  - Journal Article
PT  - Review
DEP - 20240301
PL  - United States
TA  - Exp Mol Med
JT  - Experimental & molecular medicine
JID - 9607880
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Humans
MH  - Cell Hypoxia
MH  - Hypoxia
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - *Neoplasms/pathology
MH  - *NF-E2-Related Factor 2/metabolism
MH  - Oxidative Stress
MH  - Oxygen
MH  - Tumor Microenvironment
PMC - PMC10985007
COIS- The authors declare no competing interests.
EDAT- 2024/03/01 01:27
MHDA- 2024/04/03 06:44
PMCR- 2024/03/01
CRDT- 2024/02/29 23:24
PHST- 2023/11/14 00:00 [received]
PHST- 2023/12/13 00:00 [accepted]
PHST- 2023/12/12 00:00 [revised]
PHST- 2024/04/03 06:44 [medline]
PHST- 2024/03/01 01:27 [pubmed]
PHST- 2024/02/29 23:24 [entrez]
PHST- 2024/03/01 00:00 [pmc-release]
AID - 10.1038/s12276-024-01180-8 [pii]
AID - 1180 [pii]
AID - 10.1038/s12276-024-01180-8 [doi]
PST - ppublish
SO  - Exp Mol Med. 2024 Mar;56(3):501-514. doi: 10.1038/s12276-024-01180-8. Epub 2024 
      Mar 1.