The Mechanisms of Regulation of Aerobic Glycolysis (Warburg Effect) by Oncoproteins in Carcinogenesis

被引:24
作者
Kobliakov, V. A. [1 ]
机构
[1] Minist Hlth Russia, Blokhin Canc Res Ctr, Moscow 115478, Russia
关键词
hypoxia; Warburg effect; inflammation; RAS; SRC; HIFa; MYC; mTOR; NF-KAPPA-B; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; MITOCHONDRIAL COMPLEX-III; ENDOTHELIAL GROWTH-FACTOR; CELL-CYCLE ARREST; C-MYC; CANCER-CELLS; K-RAS; DIRECT PHOSPHORYLATION; TUMOR PROGRESSION;
D O I
10.1134/S0006297919100018
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
According to modern concepts, tumor formation is associated with impairments in the structure of protooncogenes and/or deactivation of suppressor genes, regardless of the nature of carcinogenic factor. As a consequence, unregulated onco-proteins activate extracellular proteases, resulting in the destruction of the extracellular matrix, which facilitates cell invasion, deterioration of the cell-cell contacts, and metastasis. Tumor development requires activation of certain transcription factors; however, many oncoproteins are not transcription factors. It can be assumed that these oncoproteins are not the ultimate effectors of tumor development, but rather transmitters of the carcinogenic signal to the transcription factors promoting tumorigenesis. Here, we describe the mechanisms of carcinogenesis caused by various oncogenes/oncoproteins. We conclude that the common feature of these mechanisms is stimulation of aerobic glycolysis (Warburg effect) regulated, as a rule, through the activation of the HIF alpha transcription factor. The role of aerobic glycolysis at the early stages of carcinogenesis is discussed.
引用
收藏
页码:1117 / 1128
页数:12
相关论文
共 114 条
[1]   Oncogenic Ras upregulates NADPH oxidase 1 gene expression through MEK-ERK-dependent phosphorylation of GATA-6 [J].
Adachi, Y. ;
Shibai, Y. ;
Mitsushita, J. ;
Shang, W. H. ;
Hirose, K. ;
Kamata, T. .
ONCOGENE, 2008, 27 (36) :4921-4932
[2]   NADPH oxidase 5 (NOX5)induced reactive oxygen signaling modulates normoxic HIF-1 and p27Kip1 expression in malignant melanoma and other human tumors [J].
Antony, Smitha ;
Jiang, Guojian ;
Wu, Yongzhong ;
Meitzler, Jennifer L. ;
Makhlouf, Hala R. ;
Haines, Diana C. ;
Butcher, Donna ;
Hoon, Dave S. ;
Ji, Jiuping ;
Zhang, Yiping ;
Juhasz, Agnes ;
Lu, Jiamo ;
Liu, Han ;
Dahan, Iris ;
Konate, Mariam ;
Roy, Krishnendu K. ;
Doroshow, James H. .
MOLECULAR CARCINOGENESIS, 2017, 56 (12) :2643-2662
[3]   Hypoxia-induced dedifferentiation of tumor cells -: A mechanism behind heterogeneity and aggressiveness of solid tumors [J].
Axelson, H ;
Fredlund, E ;
Ovenberger, M ;
Landberg, G ;
Påhlman, S .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2005, 16 (4-5) :554-563
[4]   NF-kappa B: Ten years after [J].
Baeuerle, PA ;
Baltimore, D .
CELL, 1996, 87 (01) :13-20
[5]   HIF-1 at the crossroads of hypoxia, inflammation, and cancer [J].
Balamurugan, Kuppusamy .
INTERNATIONAL JOURNAL OF CANCER, 2016, 138 (05) :1058-1066
[6]   The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production [J].
Bell, Eric L. ;
Klimova, Tatyana A. ;
Eisenbart, James ;
Moraes, Carlos T. ;
Murphy, Michael P. ;
Budinger, G. R. Scott ;
Chandel, Navdeep S. .
JOURNAL OF CELL BIOLOGY, 2007, 177 (06) :1029-1036
[7]   HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1α in normoxia [J].
Berra, E ;
Benizri, E ;
Ginouvès, A ;
Volmat, V ;
Roux, D ;
Pouysségur, J .
EMBO JOURNAL, 2003, 22 (16) :4082-4090
[8]   Prevention of cancer by inhibiting aging [J].
Blagosklonny, Mikhail V. .
CANCER BIOLOGY & THERAPY, 2008, 7 (10) :1520-1524
[9]   NAD(P)H Oxidases regulate HIF-2α protein expression [J].
Block, Karen ;
Gorin, Yves ;
Hoover, Paul ;
Williams, Paul ;
Chelmicki, Tomasz ;
Clark, Robert A. ;
Yoneda, Toshiyuki ;
Abboud, Hanna E. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (11) :8019-8026
[10]   NADPH oxidases: not just for leukocytes anymore! [J].
Bokoch, GM ;
Knaus, UG .
TRENDS IN BIOCHEMICAL SCIENCES, 2003, 28 (09) :502-508