The Role of NRF2/KEAP1 Signaling Pathway in Cancer Metabolism

被引：105

作者：

Song, Moon-Young ^{[1
,2
]}

Lee, Da-Young ^{[1
,2
]}

Chun, Kyung-Soo ^{[3
]}

Kim, Eun-Hee ^{[1
,2
]}

机构：

[1] CHA Univ, Coll Pharm, Seongnam 13488, South Korea

[2] CHA Univ, Inst Pharmaceut Sci, Seongnam 13488, South Korea

[3] Keimyung Univ, Coll Pharm, Daegu 42601, South Korea

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2021年 / 22卷 / 09期

基金：

新加坡国家研究基金会;

关键词：

NRF2; KEAP1; cancer metabolism; metabolic reprogramming; TRANSCRIPTION FACTOR NRF2; OXIDATIVE STRESS-RESPONSE; ANTIOXIDANT RESPONSE; AMINO-ACID; MITOCHONDRIAL BIOGENESIS; NF-E2-RELATED FACTOR-2; ADAPTIVE RESPONSE; TRANSPORTER GENE; CELL METABOLISM; DOWN-REGULATION;

D O I：

10.3390/ijms22094376

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The nuclear factor-erythroid 2 p45-related factor 2 (NRF2, also called Nfe2l2) and its cytoplasmic repressor, Kelch-like ECH-associated protein 1 (KEAP1), are major regulators of redox homeostasis controlling a multiple of genes for detoxification and cytoprotective enzymes. The NRF2/KEAP1 pathway is a fundamental signaling cascade responsible for the resistance of metabolic, oxidative stress, inflammation, and anticancer effects. Interestingly, a recent accumulation of evidence has indicated that NRF2 exhibits an aberrant activation in cancer. Evidence has shown that the NRF2/KEAP1 signaling pathway is associated with the proliferation of cancer cells and tumerigenesis through metabolic reprogramming. In this review, we provide an overview of the regulatory molecular mechanism of the NRF2/KEAP1 pathway against metabolic reprogramming in cancer, suggesting that the regulation of NRF2/KEAP1 axis might approach as a novel therapeutic strategy for cancers.

引用

页数：16

共 126 条

[61] Cystine/glutamate antiporter xCT (SLC7A11) facilitates oncogenic RAS transformation by preserving intracellular redox balance [J].

Lim, Jonathan K. M. ;

Delaidelli, Alberto ;

Minaker, Sean W. ;

Zhang, Hai-Feng ;

Colovic, Milena ;

Yang, Hua ;

Negri, Gian Luca ;

von Karstedt, Silvia ;

Lockwood, William W. ;

Schaffer, Paul ;

Leprivier, Gabriel ;

Sorensen, Poul H. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2019, 116 (19) :9433-9442

[62] Hepatitis B virus stimulates G6PD expression through HBx-mediated Nrf2 activation [J].

Liu, B. ;

Fang, M. ;

He, Z. ;

Cui, D. ;

Jia, S. ;

Lin, X. ;

Xu, X. ;

Zhou, T. ;

Liu, W. .

CELL DEATH & DISEASE, 2015, 6 :e1980-e1980

[63] PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the redox-regulated keap1-dependent ubiquitin ligase complex [J].

Lo, Shih-Ching ;

Hannink, Mark .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (49) :37893-37903

[64] Structure of the Keap1: Nrf2 interface provides mechanistic insight into Nrf2 signaling [J].

Lo, Shih-Ching ;

Li, Xuchu ;

Henzl, Michael T. ;

Beamer, Lesa J. ;

Hannink, Mark .

EMBO JOURNAL, 2006, 25 (15) :3605-3617

[65] Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism [J].

Loboda, Agnieszka ;

Damulewicz, Milena ;

Pyza, Elzbieta ;

Jozkowicz, Alicja ;

Dulak, Jozef .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2016, 73 (17) :3221-3247

[66] Nrf2 affects the efficiency of mitochondrial fatty acid oxidation [J].

Ludtmann, Marthe H. R. ;

Angelova, Plamena R. ;

Zhang, Ying ;

Abramov, Andrey Y. ;

Dinkova-Kostova, Albena T. .

BIOCHEMICAL JOURNAL, 2014, 457 :415-424

[67] Aerobic Glycolysis: Meeting the Metabolic Requirements of Cell Proliferation [J].

Lunt, Sophia Y. ;

Vander Heiden, Matthew G. .

ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 27, 2011, 27 :441-464

[68] Characterization of the cancer chemopreventive NRF2-dependent gene battery in human keratinocytes: demonstration that the KEAP1-NRF2 pathway, and not the BACH1-NRF2 pathway, controls cytoprotection against electrophiles as well as redox-cycling compounds [J].

MacLeod, A. Kenneth ;

McMahon, Michael ;

Plummer, Simon M. ;

Higgins, Larry G. ;

Penning, Trevor M. ;

Igarashi, Kazuhiko ;

Hayes, John D. .

CARCINOGENESIS, 2009, 30 (09) :1571-1580

[69] The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate [J].

Maehama, T ;

Dixon, JE .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (22) :13375-13378

[70] Oxidative and electrophilic stress induces multidrug resistance-associated protein transporters via the nuclear factor-E2-related factor-2 transcriptional pathway [J].

Maher, Jonathan M. ;

Dieter, Matthew Z. ;

Aleksunes, Lauren M. ;

Slitt, Angela L. ;

Guo, Grace ;

Tanaka, Yuji ;

Scheffer, George L. ;

Chan, Jefferson Y. ;

Manautou, Jose E. ;

Chen, Ying ;

Dalton, Timothy P. ;

Yamamoto, Masayuki ;

Klaassen, Curtis D. .

HEPATOLOGY, 2007, 46 (05) :1597-1610

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