Dysregulation of the Keap1–Nrf2 pathway in cancer

2015 ◽  
Vol 43 (4) ◽  
pp. 645-649 ◽  
Author(s):  
Hanna M. Leinonen ◽  
Emilia Kansanen ◽  
Petri Pölönen ◽  
Merja Heinäniemi ◽  
Anna-Liisa Levonen
Keyword(s):  
Cancer Cells ◽  
Large Scale ◽  
Target Genes ◽  
Metabolic Reprogramming ◽  
Pivotal Role ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Pathway ◽  
Cancer Types ◽  
Constitutively Active

Accumulating evidence suggests that dysregulation of the Kelch-like ECH-associated protein 1 (Keap1)–nuclear factor E2-related factor 2 (Nrf2) pathway resulting in constitutively active Nrf2 and increased expression of cytoprotective Nrf2 target genes, has a pivotal role in cancer. Cancer cells are able to hijack the Keap1–Nrf2 system via multiple mechanisms leading to enhanced chemo- and radio-resistance and proliferation via metabolic reprogramming as well as inhibition of apoptosis. In this mini-review, we will describe the mechanisms leading to increased Nrf2 activity in cancer with a focus on the information achieved from large-scale multi-omics projects across various cancer types.

scholarly journals Small, Thin Graphene Oxide Is Anti-inflammatory Activating Nuclear Factor Erythroid 2-Related Factor 2 via Metabolic Reprogramming

ACS Nano ◽  
2018 ◽  
Vol 12 (12) ◽  
pp. 11949-11962 ◽  
Author(s):  
Christopher Hoyle ◽  
Jack Rivers-Auty ◽  
Eloïse Lemarchand ◽  
Sandra Vranic ◽  
Emily Wang ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Metabolic Reprogramming ◽  
Related Factor ◽  
Nuclear Factor ◽  
Anti Inflammatory

scholarly journals NRF2 as a regulator of cell metabolism and inflammation in cancer

2020 ◽  
Vol 41 (4) ◽  
pp. 405-416 ◽  
Author(s):  
Feng He ◽  
Laura Antonucci ◽  
Michael Karin
Keyword(s):  
Oxidative Stress ◽  
Cancer Risk ◽  
Poor Prognosis ◽  
Cell Metabolism ◽  
Transcriptional Regulator ◽  
Negative Control ◽  
Metabolic Reprogramming ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Activation

Abstract Nuclear factor erythroid 2-related factor 2 (NRF2) is a master transcriptional regulator of genes whose products defend our cells for toxic and oxidative insults. Although NRF2 activation may reduce cancer risk by suppressing oxidative stress and tumor-promoting inflammation, many cancers exhibit elevated NRF2 activity either due to mutations that disrupt the negative control of NRF2 activity or other factors. Importantly, NRF2 activation is associated with poor prognosis and NRF2 has turned out to be a key activator of cancer-supportive anabolic metabolism. In this review, we summarize the diverse roles played by NRF2 in cancer focusing on metabolic reprogramming and tumor-promoting inflammation.

scholarly journals Basic Concepts on the Role of Nuclear Factor Erythroid-Derived 2-Like 2 (Nrf2) in Age-Related Diseases

2019 ◽  
Vol 20 (13) ◽  
pp. 3208 ◽  
Author(s):  
Fabiane Valentini Francisqueti-Ferron ◽  
Artur Junio Togneri Ferron ◽  
Jéssica Leite Garcia ◽  
Carol Cristina Vágula de Almeida Silva ◽  
Mariane Róvero Costa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Transcriptional Factor ◽  
Future Research ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Pathway ◽  
Age Related ◽  
Basic Concepts

The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is one of the most important oxidative stress regulator in the human body. Once Nrf2 regulates the expression of a large number of cytoprotective genes, it plays a crucial role in the prevention of several diseases, including age-related disorders. However, the involvement of Nrf2 on these conditions is complex and needs to be clarified. Here, a brief compilation of the Nrf2 enrollment in the pathophysiology of the most common age-related diseases and bring insights for future research on the Nrf2 pathway is described. This review shows a controversial response of this transcriptional factor on the presented diseases. This reinforces the necessity of more studies to investigate modulation strategies for Nrf2, making it a possible therapeutic target in the treatment of age-related disorders.

scholarly journals The Warburg effect: 80 years on

2016 ◽  
Vol 44 (5) ◽  
pp. 1499-1505 ◽  
Author(s):  
Michelle Potter ◽  
Emma Newport ◽  
Karl J. Morten
Keyword(s):  
Cancer Cells ◽  
High Glucose ◽  
Warburg Effect ◽  
Energy Requirement ◽  
Glucose Consumption ◽  
High Energy ◽  
Metabolic Reprogramming ◽  
Normal Cells ◽  
Cancer Types ◽  
The Warburg Effect

Influential research by Warburg and Cori in the 1920s ignited interest in how cancer cells' energy generation is different from that of normal cells. They observed high glucose consumption and large amounts of lactate excretion from cancer cells compared with normal cells, which oxidised glucose using mitochondria. It was therefore assumed that cancer cells were generating energy using glycolysis rather than mitochondrial oxidative phosphorylation, and that the mitochondria were dysfunctional. Advances in research techniques since then have shown the mitochondria in cancer cells to be functional across a range of tumour types. However, different tumour populations have different bioenergetic alterations in order to meet their high energy requirement; the Warburg effect is not consistent across all cancer types. This review will discuss the metabolic reprogramming of cancer, possible explanations for the high glucose consumption in cancer cells observed by Warburg, and suggest key experimental practices we should consider when studying the metabolism of cancer.

Identification of cytokine-induced nuclear factor-kappaB target genes in ovarian and breast cancer cells

2002 ◽  
Vol 64 (5-6) ◽  
pp. 873-881 ◽  
Author(s):  
Valérie Deregowski ◽  
Sylvie Delhalle ◽  
Valérie Benoit ◽  
Vincent Bours ◽  
Marie-Paule Merville
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Target Genes ◽  
Nuclear Factor Kappab ◽  
Nuclear Factor

Nuclear factor erythroid 2-related factor 2 rescues the oxidative stress induced by di-N-butylphthalate in testicular Leydig cells

2014 ◽  
Vol 34 (2) ◽  
pp. 145-152 ◽  
Author(s):  
B Shen ◽  
W Wang ◽  
L Ding ◽  
Y Sao ◽  
Y Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Leydig Cells ◽  
Target Genes ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Quinone Oxidoreductase ◽  
Antioxidant Genes ◽  
Protein Levels

Aim: This study aimed to determine whether nuclear factor erythroid 2-related factor 2 antagonized the oxidative stress induced by di- N-butylphthalate (DBP) in testicular Leydig cells. Methods: Mouse TM3 testicular Leydig cells were treated with Nrf2 knockdown (KD) or overexpression in the presence and absence of DBP. Oxidative profiles were examined. Nrf2 target antioxidant genes were studied, and the effects of Nrf2 inducer sulphoraphane (SFN) were tested. Results: DBP induced intracellular oxidative stress to a similar extent with Nrf2 KD. Expression and protein levels of Nrf2 were increased together with its target genes, namely heme oxygenase 1, nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1 and peroxiredoxin 6, following DBP stimulation. Use of SFN not only restored the intracellular oxidative toxicity but also cell proliferation and testosterone secretion in response to DBP. Conclusion: Increased Nrf2 activity, for example, by SFN can effectively antagonize the oxidative stress in testicular Leydig cells caused by DBP.

The pivotal role of nuclear factor erythroid 2-related factor 2 in diabetes-induced endothelial dysfunction

2020 ◽  
Vol 153 ◽  
pp. 104601 ◽  
Author(s):  
Amin Karan ◽  
Elango Bhakkiyalakshmi ◽  
Ravichandran Jayasuriya ◽  
D.V.L. Sarada ◽  
Kunka Mohanram Ramkumar
Keyword(s):  
Endothelial Dysfunction ◽  
Pivotal Role ◽  
Related Factor ◽  
Nuclear Factor

scholarly journals Role of Reductive versus Oxidative Stress in Tumor Progression and Anticancer Drug Resistance

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 758
Author(s):  
Kyung-Soo Chun ◽  
Do-Hee Kim ◽  
Young-Joon Surh
Keyword(s):  
Cancer Cells ◽  
Metabolic Pathways ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Therapy Resistance ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cellular Redox ◽  
Reductive Stress

Redox homeostasis is not only essential for the maintenance of normal physiological functions, but also plays an important role in the growth, survival, and therapy resistance of cancer cells. Altered redox balance and consequent disruption of redox signaling are implicated in the proliferation and progression of cancer cells and their resistance to chemo- and radiotherapy. The nuclear factor erythroid 2 p45-related factor (Nrf2) is the principal stress-responsive transcription factor that plays a pivotal role in maintaining cellular redox homeostasis. Aberrant Nrf2 overactivation has been observed in many cancerous and transformed cells. Uncontrolled amplification of Nrf2-mediated antioxidant signaling results in reductive stress. Some metabolic pathways altered due to reductive stress have been identified as major contributors to tumorigenesis. This review highlights the multifaceted role of reductive stress in cancer development and progression.

scholarly journals Anti-Interleukin-16 Neutralizing Antibody Treatment Alleviates Sepsis-Induced Cardiac Injury and Dysfunction via the Nuclear Factor Erythroid-2 Related Factor 2 Pathway in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jianwei Zhang ◽  
Zicong Yang ◽  
Zhishan Liang ◽  
Mengjie Wang ◽  
Changxing Hu ◽  
...  
Keyword(s):  
Troponin T ◽  
Cardiac Injury ◽  
Cecal Ligation ◽  
Neutralizing Antibody ◽  
Serum Lactate ◽  
Serum Lactate Dehydrogenase ◽  
Related Factor ◽  
Nuclear Factor ◽  
Antibody Treatment ◽  
Nrf2 Pathway

Several interleukin (IL) members have been reported to participate in sepsis. In this study, the effects of IL-16 on sepsis-induced cardiac injury and dysfunction were examined, and the related mechanisms were detected. IL-16 expression in septic mice was first measured, and the results showed that both cardiac and serum IL-16 expression levels were increased in mice with sepsis induced by LPS or cecal ligation and puncture (CLP) compared with control mice. Then, IL-16 was neutralized, and the effects on lipopolysaccharide- (LPS-) induced cardiac injury were detected. The results showed that an anti-IL-16 neutralizing antibody (nAb) significantly reduced mortality and increased serum lactate dehydrogenase (LDH), creatine kinase myocardial bound (CK-MB), and cardiac troponin T (cTnT) levels while improving cardiac function in mice with LPS-induced sepsis. Neutralization of IL-16 also increased the activation of antioxidant pathways and the expression of antioxidant factors in septic mice while decreasing the activation of prooxidant pathways and the expression of prooxidants. Treatment with the anti-IL-16 nAb increased mitochondrial apoptosis-inducing factor (AIF) expression, decreased nuclear AIF and cleaved poly-ADP-ribose polymerase (PARP) expression, and decreased TUNEL-positive cell percentages in LPS-treated mice. Additionally, treatment with CPUY192018, the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway, significantly increased mortality and reversed the above effects in mice treated with LPS and the anti-IL-16 nAb. Our results showed that the anti-IL-16 nAb regulates oxidative stress through the Nrf2 pathway and participates in the regulation of cardiac injury in septic mice. Neutralization of IL-16 may be a beneficial strategy for the prevention of cardiac injury and dysfunction in sepsis patients.

scholarly journals Promoter demethylation of nuclear factor-erythroid 2-related factor 2 gene in drug-resistant colon cancer cells

2015 ◽  
Vol 10 (3) ◽  
pp. 1287-1292 ◽  
Author(s):  
XIAO-QIAN ZHAO ◽  
YI-FEI ZHANG ◽  
YI-FANG XIA ◽  
ZHONG-MEI ZHOU ◽  
YING-QING CAO
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Related Factor ◽  
Nuclear Factor ◽  
Drug Resistant ◽  
Colon Cancer Cells
Sign in / Sign up

Export Citation Format

Share Document