The Control of the Metabolic Switch in Cancers by Oncogenes and Tumor Suppressor Genes

被引：1007

作者：

Levine, Arnold J. ^{[1
,2
]}

Puzio-Kuter, Anna M. ^{[2
]}

机构：

[1] Inst Adv Study, Princeton, NJ 08540 USA

[2] Canc Inst New Jersey, New Brunswick, NJ 08903 USA

来源：

SCIENCE | 2010年 / 330卷 / 6009期

关键词：

CELL-GROWTH; P53-INDUCIBLE REGULATOR; GLUTAMINE-METABOLISM; DIABETIC-PATIENTS; P53; METFORMIN; PROTEIN; GLYCOLYSIS; APOPTOSIS; PATHWAYS;

D O I：

10.1126/science.1193494

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cells from some tumors use an altered metabolic pattern compared with that of normal differentiated adult cells in the body. Tumor cells take up much more glucose and mainly process it through aerobic glycolysis, producing large quantities of secreted lactate with a lower use of oxidative phosphorylation that would generate more adenosine triphosphate (ATP), water, and carbon dioxide. This is the Warburg effect, which provides substrates for cell growth and division and free energy (ATP) from enhanced glucose use. This metabolic switch places the emphasis on producing intermediates for cell growth and division, and it is regulated by both oncogenes and tumor suppressor genes in a number of key cancer-producing pathways. Blocking these metabolic pathways or restoring these altered pathways could lead to a new approach in cancer treatments.

引用

页码：1340 / 1344

页数：5

共 39 条

[1] p53 and NF-κB: different strategies for responding to stress lead to a functional antagonism [J].

Ak, Prashanth ;

Levine, Arnold J. .

FASEB JOURNAL, 2010, 24 (10) :3643-3652

[2] TIGAR, a p53-inducible regulator of glycolysis and apoptosis [J].

Bensaad, Karim ;

Tsuruta, Atsushi ;

Selak, Mary A. ;

Calvo Vidal, M. Nieves ;

Nakano, Katsunori ;

Bartrons, Ramon ;

Gottlieb, Eyal ;

Vousden, Karen H. .

CELL, 2006, 126 (01) :107-120

[3] Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion [J].

Bourdon, Alice ;

Minai, Limor ;

Serre, Valerie ;

Jais, Jean-Philippe ;

Sarzi, Emmanuelle ;

Aubert, Sophie ;

Chretien, Dominique ;

de Lonlay, Pascale ;

Paquis-Flucklinger, Veronique ;

Arakawa, Hirofumi ;

Nakamura, Yusuke ;

Munnich, Arnold ;

Rotig, Agnes .

NATURE GENETICS, 2007, 39 (06) :776-780

[4] A conserved family of prolyl-4-hydroxylases that modify HIF [J].

Bruick, RK ;

McKnight, SL .

SCIENCE, 2001, 294 (5545) :1337-1340

[5] p53 target genes Sestrin1 and Sestrin2 connect genotoxic stress and mTOR signaling [J].

Budanov, Andrei V. ;

Karin, Michael .

CELL, 2008, 134 (03) :451-460

[6] Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD [J].

Budanov, AV ;

Sablina, AA ;

Feinstein, E ;

Koonin, EV ;

Chumakov, PM .

SCIENCE, 2004, 304 (5670) :596-600

[7] Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth [J].

Buzzai, Monica ;

Jones, Russell G. ;

Amaravadi, Ravi K. ;

Lum, Julian J. ;

DeBerardinis, Ralph J. ;

Zhao, Fangping ;

Viollet, Benoit ;

Thompson, Craig B. .

CANCER RESEARCH, 2007, 67 (14) :6745-6752

[8] Pyruvate kinase M2 is a phosphotyrosine-binding protein [J].

Christofk, Heather R. ;

Vander Heiden, Matthew G. ;

Wu, Ning ;

Asara, John M. ;

Cantley, Lewis C. .

NATURE, 2008, 452 (7184) :181-U27

[9]

Dang CV, 1999, MOL CELL BIOL, V19, P1

[10] Cancer-associated IDH1 mutations produce 2-hydroxyglutarate (vol 462, pg 739, 2010) [J].

Dang, Lenny ;

White, David W. ;

Gross, Stefan ;

Bennett, Bryson D. ;

Bittinger, Mark A. ;

Driggers, Edward M. ;

Fantin, Valeria R. ;

Jang, Hyun Gyung ;

Jin, Shengfang ;

Keenan, Marie C. ;

Marks, Kevin M. ;

Prins, Robert M. ;

Ward, Patrick S. ;

Yen, Katharine E. ;

Liau, Linda M. ;

Rabinowitz, Joshua D. ;

Cantley, Lewis C. ;

Thompson, Craig B. ;

Vander Heiden, Matthew G. ;

Su, Shinsan M. .

NATURE, 2010, 465 (7300) :966-966

← 1 2 3 4 →