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Reactive Oxygen Species and NRF2 Signaling, Friends or Foes in Cancer?

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 ca...

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Autores principales: Wang, Ruolei, Liang, Lirong, Matsumoto, Misaki, Iwata, Kazumi, Umemura, Atsushi, He, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953152/
https://www.ncbi.nlm.nih.gov/pubmed/36830722
http://dx.doi.org/10.3390/biom13020353
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author Wang, Ruolei
Liang, Lirong
Matsumoto, Misaki
Iwata, Kazumi
Umemura, Atsushi
He, Feng
author_facet Wang, Ruolei
Liang, Lirong
Matsumoto, Misaki
Iwata, Kazumi
Umemura, Atsushi
He, Feng
author_sort Wang, Ruolei
collection PubMed
description 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.
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spelling pubmed-99531522023-02-25 Reactive Oxygen Species and NRF2 Signaling, Friends or Foes in Cancer? Wang, Ruolei Liang, Lirong Matsumoto, Misaki Iwata, Kazumi Umemura, Atsushi He, Feng Biomolecules Review 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. MDPI 2023-02-11 /pmc/articles/PMC9953152/ /pubmed/36830722 http://dx.doi.org/10.3390/biom13020353 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Wang, Ruolei
Liang, Lirong
Matsumoto, Misaki
Iwata, Kazumi
Umemura, Atsushi
He, Feng
Reactive Oxygen Species and NRF2 Signaling, Friends or Foes in Cancer?
title Reactive Oxygen Species and NRF2 Signaling, Friends or Foes in Cancer?
title_full Reactive Oxygen Species and NRF2 Signaling, Friends or Foes in Cancer?
title_fullStr Reactive Oxygen Species and NRF2 Signaling, Friends or Foes in Cancer?
title_full_unstemmed Reactive Oxygen Species and NRF2 Signaling, Friends or Foes in Cancer?
title_short Reactive Oxygen Species and NRF2 Signaling, Friends or Foes in Cancer?
title_sort reactive oxygen species and nrf2 signaling, friends or foes in cancer?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953152/
https://www.ncbi.nlm.nih.gov/pubmed/36830722
http://dx.doi.org/10.3390/biom13020353
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