Cancer Research 09 AM Call for Abstracts SU2C
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Elstrom, R. L.
Right arrow Articles by Thompson, C. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Elstrom, R. L.
Right arrow Articles by Thompson, C. B.
[Cancer Research 64, 3892-3899, June 1, 2004]
© 2004 American Association for Cancer Research

Regular Articles

Akt Stimulates Aerobic Glycolysis in Cancer Cells

Rebecca L. Elstrom1, Daniel E. Bauer1, Monica Buzzai1, Robyn Karnauskas3, Marian H. Harris1, David R. Plas1, Hongming Zhuang2, Ryan M. Cinalli1, Abass Alavi2, Charles M. Rudin4 and Craig B. Thompson1

1 Abramson Family Cancer Research Institute, Department of Cancer Biology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; 2 Division of Nuclear Medicine, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania; 3 Department of Medicine, University of Chicago, Chicago, Illinois; and 4 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland

Cancer cells frequently display high rates of aerobic glycolysis in comparison to their nontransformed counterparts, although the molecular basis of this phenomenon remains poorly understood. Constitutive activity of the serine/threonine kinase Akt is a common perturbation observed in malignant cells. Surprisingly, although Akt activity is sufficient to promote leukemogenesis in nontransformed hematopoietic precursors and maintenance of Akt activity was required for rapid disease progression, the expression of activated Akt did not increase the proliferation of the premalignant or malignant cells in culture. However, Akt stimulated glucose consumption in transformed cells without affecting the rate of oxidative phosphorylation. High rates of aerobic glycolysis were also identified in human glioblastoma cells possessing but not those lacking constitutive Akt activity. Akt-expressing cells were more susceptible than control cells to death after glucose withdrawal. These data suggest that activation of the Akt oncogene is sufficient to stimulate the switch to aerobic glycolysis characteristic of cancer cells and that Akt activity renders cancer cells dependent on aerobic glycolysis for continued growth and survival.




This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
D. R. Wise, R. J. DeBerardinis, A. Mancuso, N. Sayed, X.-Y. Zhang, H. K. Pfeiffer, I. Nissim, E. Daikhin, M. Yudkoff, S. B. McMahon, et al.
Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction
PNAS, December 2, 2008; 105(48): 18782 - 18787.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
M. A. Kiebish, X. Han, H. Cheng, J. H. Chuang, and T. N. Seyfried
Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer
J. Lipid Res., December 1, 2008; 49(12): 2545 - 2556.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. Marsh, P. Mukherjee, and T. N. Seyfried
Akt-Dependent Proapoptotic Effects of Dietary Restriction on Late-Stage Management of a Phosphatase and Tensin Homologue/Tuberous Sclerosis Complex 2-Deficient Mouse Astrocytoma
Clin. Cancer Res., December 1, 2008; 14(23): 7751 - 7762.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Migita, T. Narita, K. Nomura, E. Miyagi, F. Inazuka, M. Matsuura, M. Ushijima, T. Mashima, H. Seimiya, Y. Satoh, et al.
ATP Citrate Lyase: Activation and Therapeutic Implications in Non-Small Cell Lung Cancer
Cancer Res., October 15, 2008; 68(20): 8547 - 8554.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. C. F. Hsieh, D. Das, N. Sambandam, M. Q. Zhang, and Z. Nahle
Regulation of the PDK4 Isozyme by the Rb-E2F1 Complex
J. Biol. Chem., October 10, 2008; 283(41): 27410 - 27417.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
N. J. MacIver, S. R. Jacobs, H. L. Wieman, J. A. Wofford, J. L. Coloff, and J. C. Rathmell
Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival
J. Leukoc. Biol., October 1, 2008; 84(4): 949 - 957.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
E. D. Michelakis, M. R. Wilkins, and M. Rabinovitch
Emerging Concepts and Translational Priorities in Pulmonary Arterial Hypertension
Circulation, September 30, 2008; 118(14): 1486 - 1495.
[Full Text] [PDF]

Home page
 Hum Mol GenetHome page
G. P. Lobo, K. A. Waite, S. M. Planchon, T. Romigh, J. A. Houghton, and C. Eng
ATP modulates PTEN subcellular localization in multiple cancer cell lines
Hum. Mol. Genet., September 15, 2008; 17(18): 2877 - 2885.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. McFate, A. Mohyeldin, H. Lu, J. Thakar, J. Henriques, N. D. Halim, H. Wu, M. J. Schell, T. M. Tsang, O. Teahan, et al.
Pyruvate Dehydrogenase Complex Activity Controls Metabolic and Malignant Phenotype in Cancer Cells
J. Biol. Chem., August 15, 2008; 283(33): 22700 - 22708.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
X. Jiang, H. Kenerson, L. Aicher, R. Miyaoka, J. Eary, J. Bissler, and R. S. Yeung
The Tuberous Sclerosis Complex Regulates Trafficking of Glucose Transporters and Glucose Uptake
Am. J. Pathol., June 1, 2008; 172(6): 1748 - 1756.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
R. J. Gillies, I. Robey, and R. A. Gatenby
Causes and Consequences of Increased Glucose Metabolism of Cancers
J. Nucl. Med., June 1, 2008; 49(Suppl_2): 24S - 42S.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
C. Plathow and W. A. Weber
Tumor Cell Metabolism Imaging
J. Nucl. Med., June 1, 2008; 49(Suppl_2): 43S - 63S.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
D. Zhong, X. Liu, K. Schafer-Hales, A. I. Marcus, F. R. Khuri, S.-Y. Sun, and W. Zhou
2-Deoxyglucose induces Akt phosphorylation via a mechanism independent of LKB1/AMP-activated protein kinase signaling activation or glycolysis inhibition
Mol. Cancer Ther., April 1, 2008; 7(4): 809 - 817.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
F. B. Furnari, T. Fenton, R. M. Bachoo, A. Mukasa, J. M. Stommel, A. Stegh, W. C. Hahn, K. L. Ligon, D. N. Louis, C. Brennan, et al.
Malignant astrocytic glioma: genetics, biology, and paths to treatment
Genes & Dev., November 1, 2007; 21(21): 2683 - 2710.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
H. Ono, H. Sakoda, M. Fujishiro, M. Anai, A. Kushiyama, Y. Fukushima, H. Katagiri, T. Ogihara, Y. Oka, H. Kamata, et al.
Carboxy-terminal modulator protein induces Akt phosphorylation and activation, thereby enhancing antiapoptotic, glycogen synthetic, and glucose uptake pathways
Am J Physiol Cell Physiol, November 1, 2007; 293(5): C1576 - C1585.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. Ursini-Siegel, A. B. Rajput, H. Lu, V. Sanguin-Gendreau, D. Zuo, V. Papavasiliou, C. Lavoie, J. Turpin, K. Cianflone, D. G. Huntsman, et al.
Elevated Expression of DecR1 Impairs ErbB2/Neu-Induced Mammary Tumor Development
Mol. Cell. Biol., September 15, 2007; 27(18): 6361 - 6371.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
N. L. Spector, Y. Yarden, B. Smith, L. Lyass, P. Trusk, K. Pry, J. E. Hill, W. Xia, R. Seger, and S. S. Bacus
Activation of AMP-activated protein kinase by human EGF receptor 2/EGF receptor tyrosine kinase inhibitor protects cardiac cells
PNAS, June 19, 2007; 104(25): 10607 - 10612.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
A. M. Sargeant, R. D. Klein, R. C. Rengel, S. K. Clinton, S. K. Kulp, Y. Kashida, M. Yamaguchi, X. Wang, and C.-S. Chen
Chemopreventive and Bioenergetic Signaling Effects of PDK1/Akt Pathway Inhibition in a Transgenic Mouse Model of Prostate Cancer
Toxicol Pathol, June 1, 2007; 35(4): 549 - 561.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. A. Cairns, I. Papandreou, P. D. Sutphin, and N. C. Denko
Metabolic targeting of hypoxia and HIF1 in solid tumors can enhance cytotoxic chemotherapy
PNAS, May 29, 2007; 104(22): 9445 - 9450.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. M. Funes, M. Quintero, S. Henderson, D. Martinez, U. Qureshi, C. Westwood, M. O. Clements, D. Bourboulia, R. B. Pedley, S. Moncada, et al.
Transformation of human mesenchymal stem cells increases their dependency on oxidative phosphorylation for energy production
PNAS, April 10, 2007; 104(15): 6223 - 6228.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
S. Jin, R. S. DiPaola, R. Mathew, and E. White
Metabolic catastrophe as a means to cancer cell death
J. Cell Sci., February 1, 2007; 120(3): 379 - 383.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
W. A. Weber and R. Figlin
Monitoring Cancer Treatment with PET/CT: Does It Make a Difference?
J. Nucl. Med., January 1, 2007; 48(1_suppl): 36S - 44S.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
M. Wu, A. Neilson, A. L. Swift, R. Moran, J. Tamagnine, D. Parslow, S. Armistead, K. Lemire, J. Orrell, J. Teich, et al.
Multiparameter metabolic analysis reveals a close link between attenuated mitochondrial bioenergetic function and enhanced glycolysis dependency in human tumor cells
Am J Physiol Cell Physiol, January 1, 2007; 292(1): C125 - C136.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
H. Pelicano, R.-h. Xu, M. Du, L. Feng, R. Sasaki, J. S. Carew, Y. Hu, L. Ramdas, L. Hu, M. J. Keating, et al.
Mitochondrial respiration defects in cancer cells cause activation of Akt survival pathway through a redox-mediated mechanism
J. Cell Biol., December 18, 2006; 175(6): 913 - 923.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. J. DeBerardinis, J. J. Lum, and C. B. Thompson
Phosphatidylinositol 3-Kinase-dependent Modulation of Carnitine Palmitoyltransferase 1A Expression Regulates Lipid Metabolism during Hematopoietic Cell Growth
J. Biol. Chem., December 8, 2006; 281(49): 37372 - 37380.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. G.M. van Gorp, K. M. Pomeranz, K. U. Birkenkamp, R. C-Y. Hui, E. W-F. Lam, and P. J. Coffer
Chronic Protein Kinase B (PKB/c-akt) Activation Leads to Apoptosis Induced by Oxidative Stress-Mediated Foxo3a Transcriptional Up-regulation.
Cancer Res., November 15, 2006; 66(22): 10760 - 10769.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. M. Kornblau, M. Womble, Y. H. Qiu, C. E. Jackson, W. Chen, M. Konopleva, E. H. Estey, and M. Andreeff
Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia
Blood, October 1, 2006; 108(7): 2358 - 2365.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J.-w. Kim and C. V. Dang
Cancer's Molecular Sweet Tooth and the Warburg Effect.
Cancer Res., September 15, 2006; 66(18): 8927 - 8930.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S.-H. Jo, C. Yang, Q. Miao, M. Marzec, M. A. Wasik, P. Lu, and Y. L. Wang
Peroxisome Proliferator-Activated Receptor {gamma} Promotes Lymphocyte Survival through Its Actions on Cellular Metabolic Activities
J. Immunol., September 15, 2006; 177(6): 3737 - 3745.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. I. Koukourakis, A. Giatromanolaki, E. Sivridis, K. C. Gatter, and A. L. Harris
Lactate Dehydrogenase 5 Expression in Operable Colorectal Cancer: Strong Association With Survival and Activated Vascular Endothelial Growth Factor Pathway--A Report of the Tumour Angiogenesis Research Group
J. Clin. Oncol., September 10, 2006; 24(26): 4301 - 4308.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Bagheri, M. Nosrati, S. Li, S. Fong, S. Torabian, J. Rangel, D. H. Moore, S. Federman, R. R. LaPosa, F. L. Baehner, et al.
Genes and pathways downstream of telomerase in melanoma metastasis
PNAS, July 25, 2006; 103(30): 11306 - 11311.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. S. Yi, B. C. Holbrook, R. D. Michalek, N. G. Laniewski, and J. M. Grayson
Electron Transport Complex I Is Required for CD8+ T Cell Function
J. Immunol., July 15, 2006; 177(2): 852 - 862.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
W. A. Weber
Positron Emission Tomography As an Imaging Biomarker
J. Clin. Oncol., July 10, 2006; 24(20): 3282 - 3292.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
S. Matoba, J.-G. Kang, W. D. Patino, A. Wragg, M. Boehm, O. Gavrilova, P. J. Hurley, F. Bunz, and P. M. Hwang
p53 Regulates Mitochondrial Respiration
Science, June 16, 2006; 312(5780): 1650 - 1653.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
N. Jelluma, X. Yang, D. Stokoe, G. I. Evan, T. B. Dansen, and D. A. Haas-Kogan
Glucose Withdrawal Induces Oxidative Stress followed by Apoptosis in Glioblastoma Cells but not in Normal Human Astrocytes
Mol. Cancer Res., May 1, 2006; 4(5): 319 - 330.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. I. Koukourakis, A. Giatromanolaki, A. L. Harris, and E. Sivridis
Comparison of Metabolic Pathways between Cancer Cells and Stromal Cells in Colorectal Carcinomas: a Metabolic Survival Role for Tumor-Associated Stroma
Cancer Res., January 15, 2006; 66(2): 632 - 637.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
A. Isidoro, E. Casado, A. Redondo, P. Acebo, E. Espinosa, A. M. Alonso, P. Cejas, D. Hardisson, J. A. Fresno Vara, C. Belda-Iniesta, et al.
Breast carcinomas fulfill the Warburg hypothesis and provide metabolic markers of cancer prognosis
Carcinogenesis, December 1, 2005; 26(12): 2095 - 2104.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
M. P. Biju, Y. Akai, N. Shrimanker, and V. H. Haase
Protection of HIF-1-deficient primary renal tubular epithelial cells from hypoxia-induced cell death is glucose dependent
Am J Physiol Renal Physiol, December 1, 2005; 289(6): F1217 - F1226.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. G. Pastorino, J. B. Hoek, and N. Shulga
Activation of Glycogen Synthase Kinase 3{beta} Disrupts the Binding of Hexokinase II to Mitochondria by Phosphorylating Voltage-Dependent Anion Channel and Potentiates Chemotherapy-Induced Cytotoxicity
Cancer Res., November 15, 2005; 65(22): 10545 - 10554.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Cullinane, D. S. Dorow, M. Kansara, N. Conus, D. Binns, R. J. Hicks, L. K. Ashman, G. A. McArthur, and D. M. Thomas
An In vivo Tumor Model Exploiting Metabolic Response as a Biomarker for Targeted Drug Development
Cancer Res., November 1, 2005; 65(21): 9633 - 9636.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
D. J. VanderWeele and C. M. Rudin
Mammalian Target of Rapamycin Promotes Vincristine Resistance through Multiple Mechanisms Independent of Maintained Glycolytic Rate
Mol. Cancer Res., November 1, 2005; 3(11): 635 - 644.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
J. D. Lee, W. I. Yang, Y. N. Park, K. S. Kim, J. S. Choi, M. Yun, D. Ko, T.-S. Kim, A. E.H. Cho, H. M. Kim, et al.
Different Glucose Uptake and Glycolytic Mechanisms Between Hepatocellular Carcinoma and Intrahepatic Mass-Forming Cholangiocarcinoma with Increased 18F-FDG Uptake
J. Nucl. Med., October 1, 2005; 46(10): 1753 - 1759.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
W. A. Weber
Use of PET for Monitoring Cancer Therapy and for Predicting Outcome
J. Nucl. Med., June 1, 2005; 46(6): 983 - 995.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Ramanathan, C. Wang, and S. L. Schreiber
Perturbational profiling of a cell-line model of tumorigenesis by using metabolic measurements
PNAS, April 26, 2005; 102(17): 5992 - 5997.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. J. Kelloff, J. M. Hoffman, B. Johnson, H. I. Scher, B. A. Siegel, E. Y. Cheng, B. D. Cheson, J. O'Shaughnessy, K. Z. Guyton, D. A. Mankoff, et al.
Progress and Promise of FDG-PET Imaging for Cancer Patient Management and Oncologic Drug Development
Clin. Cancer Res., April 15, 2005; 11(8): 2785 - 2808.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. Govindarajan, A. Shah, C. Cohen, R. S. Arnold, J. Schechner, J. Chung, A. M. Mercurio, R. Alani, B. Ryu, C.-Y. Fan, et al.
Malignant Transformation of Human Cells by Constitutive Expression of Platelet-derived Growth Factor-BB
J. Biol. Chem., April 8, 2005; 280(14): 13936 - 13943.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
D. J. VanderWeele, R. Zhou, and C. M. Rudin
Akt up-regulation increases resistance to microtubule-directed chemotherapeutic agents through mammalian target of rapamycin
Mol. Cancer Ther., December 1, 2004; 3(12): 1605 - 1613.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2004 by the American Association for Cancer Research.