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
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
收藏
页数:16
相关论文
共 126 条
[1]   Renal Cyst Formation in Fh1-Deficient Mice Is Independent of the Hif/Phd Pathway: Roles for Fumarate in KEAP1 Succination and Nrf2 Signaling [J].
Adam, Julie ;
Hatipoglu, Emine ;
O'Flaherty, Linda ;
Ternette, Nicola ;
Sahgal, Natasha ;
Lockstone, Helen ;
Baban, Dilair ;
Nye, Emma ;
Stamp, Gordon W. ;
Wolhuter, Kathryn ;
Stevens, Marcus ;
Fischer, Roman ;
Carmeliet, Peter ;
Maxwell, Patrick H. ;
Pugh, Chris W. ;
Frizzell, Norma ;
Soga, Tomoyoshi ;
Kessler, Benedikt M. ;
El-Bahrawy, Mona ;
Ratcliffe, Peter J. ;
Pollard, Patrick J. .
CANCER CELL, 2011, 20 (04) :524-537
[2]   Transcriptomic and proteomic profiling of KEAP1 disrupted and sulforaphane-treated human breast epithelial cells reveals common expression profiles [J].
Agyeman, Abena S. ;
Chaerkady, Raghothama ;
Shaw, Patrick G. ;
Davidson, Nancy E. ;
Visvanathan, Kala ;
Pandey, Akhilesh ;
Kensler, Thomas W. .
BREAST CANCER RESEARCH AND TREATMENT, 2012, 132 (01) :175-187
[3]   Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency [J].
Alam, NA ;
Rowan, AJ ;
Wortham, NC ;
Pollard, PJ ;
Mitchell, M ;
Tyrer, JP ;
Barclay, E ;
Calonje, E ;
Manek, S ;
Adams, SJ ;
Bowers, PW ;
Burrows, NP ;
Charles-Holmes, R ;
Cook, LJ ;
Daly, BM ;
Ford, GP ;
Fuller, LC ;
Hadfield-Jones, SE ;
Hardwick, N ;
Highet, AS ;
Keefe, M ;
MacDonald-Hull, SP ;
Potts, EDA ;
Crone, M ;
Wilkinson, S ;
Camacho-Martinez, F ;
Jablonska, S ;
Ratnavel, R ;
MacDonald, A ;
Mann, RJ ;
Grice, K ;
Guillet, G ;
Lewis-Jones, MS ;
McGrath, H ;
Seukeran, DC ;
Morrison, PJ ;
Fleming, S ;
Rahman, S ;
Kelsell, D ;
Leigh, I ;
Olpin, S ;
Tomlinson, IPM .
HUMAN MOLECULAR GENETICS, 2003, 12 (11) :1241-1252
[4]   Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development [J].
Baenke, Franziska ;
Peck, Barrie ;
Miess, Heike ;
Schulze, Almut .
DISEASE MODELS & MECHANISMS, 2013, 6 (06) :1353-1363
[5]   The cytoprotective role of the Keap1-Nrf2 pathway [J].
Baird, Liam ;
Dinkova-Kostova, Albena T. .
ARCHIVES OF TOXICOLOGY, 2011, 85 (04) :241-272
[6]   New aspects of the Warburg effect in cancer cell biology [J].
Bensinger, Steven J. ;
Christofk, Heather R. .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2012, 23 (04) :352-361
[7]   A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2 signalling [J].
Bollong, Michael J. ;
Lee, Gihoon ;
Coukos, John S. ;
Yun, Hwayoung ;
Zambaldo, Claudio ;
Chang, Jae Won ;
Chin, Emily N. ;
Ahmad, Insha ;
Chatterjee, Arnab K. ;
Lairson, Luke L. ;
Schultz, Peter G. ;
Moellering, Raymond E. .
NATURE, 2018, 562 (7728) :600-+
[8]   Metabolic pathways promoting cancer cell survival and growth [J].
Boroughs, Lindsey K. ;
DeBerardinis, Ralph J. .
NATURE CELL BIOLOGY, 2015, 17 (04) :351-359
[9]   Structural basis of Keap1 interactions with Nrf2 [J].
Canning, Peter ;
Sorrell, Fiona J. ;
Bullock, Alex N. .
FREE RADICAL BIOLOGY AND MEDICINE, 2015, 88 :101-107
[10]   Cancer Cell Metabolism: One Hallmark, Many Faces [J].
Cantor, Jason R. ;
Sabatini, David M. .
CANCER DISCOVERY, 2012, 2 (10) :881-898