The Warburg effect then and now: From cancer to inflammatory diseases

被引：417

作者：

Palsson-McDermott, Eva M. ^{[1
]}

O'Neill, Luke A. J. ^{[1
]}

机构：

[1] Univ Dublin Trinity Coll, Sch Biochem & Immunol, Dublin 2, Ireland

来源：

BIOESSAYS | 2013年 / 35卷 / 11期

关键词：

Hif-1; glycolysis; inflammation; metabolism; PKM2; TLR; Warburg effect; PYRUVATE-KINASE M2; HYPOXIA-INDUCIBLE FACTOR-1; ACTIVATED PROTEIN-KINASE; TUMOR-GROWTH; T-CELLS; DEHYDROGENASE KINASE; GLUCOSE-METABOLISM; IN-VITRO; DICHLOROACETATE; METFORMIN;

D O I：

10.1002/bies.201300084

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：

Inflammatory immune cells, when activated, display much the same metabolic profile as a glycolytic tumor cell. This involves a shift in metabolism away from oxidative phosphorylation towards aerobic glycolysis, a phenomenon known as the Warburg effect. The result of this change in macrophages is to rapidly provide ATP and metabolic intermediates for the biosynthesis of immune and inflammatory proteins. In addition, a rise in certain tricarboxylic acid cycle intermediates occurs notably in citrate for lipid biosynthesis, and succinate, which activates the transcription factor Hypoxia-inducible factor. In this review we take a look at the emerging evidence for a role for the Warburg effect in the immune and inflammatory responses. The reprogramming of metabolic pathways in macrophages, dendritic cells, and T cells could have relevance in the pathogenesis of inflammatory and metabolic diseases and might provide novel therapeutic strategies.

引用

页码：965 / 973

页数：9

共 73 条

[1] Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis [J].

Anastasiou, Dimitrios ;

Yu, Yimin ;

Israelsen, William J. ;

Jiang, Jian-Kang ;

Boxer, Matthew B. ;

Hong, Bum Soo ;

Tempel, Wolfram ;

Dimov, Svetoslav ;

Shen, Min ;

Jha, Abhishek ;

Yang, Hua ;

Mattaini, Katherine R. ;

Metallo, Christian M. ;

Fiske, Brian P. ;

Courtney, Kevin D. ;

Malstrom, Scott ;

Khan, Tahsin M. ;

Kung, Charles ;

Skoumbourdis, Amanda P. ;

Veith, Henrike ;

Southall, Noel ;

Walsh, Martin J. ;

Brimacombe, Kyle R. ;

Leister, William ;

Lunt, Sophia Y. ;

Johnson, Zachary R. ;

Yen, Katharine E. ;

Kunii, Kaiko ;

Davidson, Shawn M. ;

Christofk, Heather R. ;

Austin, Christopher P. ;

Inglese, James ;

Harris, Marian H. ;

Asara, John M. ;

Stephanopoulos, Gregory ;

Salituro, Francesco G. ;

Jin, Shengfang ;

Dang, Lenny ;

Auld, Douglas S. ;

Park, Hee-Won ;

Cantley, Lewis C. ;

Thomas, Craig J. ;

Heiden, Matthew G. Vander .

NATURE CHEMICAL BIOLOGY, 2012, 8 (10) :839-847

[2] Metformin in Cancer Therapy: A New Perspective for an Old Antidiabetic Drug? [J].

Ben Sahra, Issam ;

Le Marchand-Brustel, Yannick ;

Tanti, Jean-Francois ;

Bost, Frederic .

MOLECULAR CANCER THERAPEUTICS, 2010, 9 (05) :1092-1099

[3] Temsirolimus: a safety and efficacy review [J].

Bukowski, Ronald M. .

EXPERT OPINION ON DRUG SAFETY, 2012, 11 (05) :861-879

[4] Regulation of cancer cell metabolism [J].

Cairns, Rob A. ;

Harris, Isaac S. ;

Mak, Tak W. .

NATURE REVIEWS CANCER, 2011, 11 (02) :85-95

[5] Dichloroacetate (DCA) sensitizes both wild-type and over expressing Bcl-2 prostate cancer cells in vitro to radiation [J].

Cao, Wengang ;

Yacoub, Saif ;

Shiverick, Kathleen T. ;

Namiki, Kazunori ;

Sakai, Yoshihisa ;

Porvasnik, Stacy ;

Urbanek, Cydney ;

Rosser, Charles J. .

PROSTATE, 2008, 68 (11) :1223-1231

[6] Two Phase 2 Trials of the Novel Akt Inhibitor Perifosine in Patients With Advanced Renal Cell Carcinoma After Progression on Vascular Endothelial Growth Factor-Targeted Therapy [J].

Cho, Daniel C. ;

Hutson, Thomas E. ;

Samlowski, Wolfram ;

Sportelli, Peter ;

Somer, Brad ;

Richards, Paul ;

Sosman, Jeffrey A. ;

Puzanov, Igor ;

Michaelson, M. Dror ;

Flaherty, Keith T. ;

Figlin, Robert A. ;

Vogelzang, Nicholas J. .

CANCER, 2012, 118 (24) :6055-6062

[7] The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth [J].

Christofk, Heather R. ;

Vander Heiden, Matthew G. ;

Harris, Marian H. ;

Ramanathan, Arvind ;

Gerszten, Robert E. ;

Wei, Ru ;

Fleming, Mark D. ;

Schreiber, Stuart L. ;

Cantley, Lewis C. .

NATURE, 2008, 452 (7184) :230-U74

[8] AMPK: opposing the metabolic changes in both tumour cells and inflammatory cells? [J].

Dandapani, Madhumita ;

Hardie, D. Grahame .

BIOCHEMICAL SOCIETY TRANSACTIONS, 2013, 41 :687-693

[9] Control of TH17/Treg Balance by Hypoxia-Inducible Factor 1 [J].

Dang, Eric V. ;

Barbi, Joseph ;

Yang, Huang-Yu ;

Jinasena, Dilini ;

Yu, Hong ;

Zheng, Ying ;

Bordman, Zachary ;

Fu, Juan ;

Kim, Young ;

Yen, Hung-Rong ;

Luo, Weibo ;

Zeller, Karen ;

Shimoda, Larissa ;

Topalian, Suzanne L. ;

Semenza, Gregg L. ;

Dang, Chi V. ;

Pardoll, Drew M. ;

Pan, Fan .

CELL, 2011, 146 (05) :772-784

[10] Epstein-Barr Virus Immortalization of Human B-Cells Leads to Stabilization of Hypoxia-Induced Factor 1 Alpha, Congruent with the Warburg Effect [J].

Darekar, Suhas ;

Georgiou, Konstantinos ;

Yurchenko, Mariya ;

Yenamandra, Surya Pavan ;

Chachami, Georgia ;

Simos, George ;

Klein, George ;

Kashuba, Elena .

PLOS ONE, 2012, 7 (07)

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