QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online January 24, 2007
doi: 10.1242/10.1242/jcs.03349

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jin, S. Articles by White, E. Search for Related Content PubMed PubMed Citation Articles by Jin, S. Articles by White, E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Cancer Hazardous Substances DB GLUCOSE Social Bookmarking                         What's this?

Metabolic catastrophe as a means to cancer cell death

¹ Department of Pharmacology, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA
² University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA
³ Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA
⁴ Department of Medicine, 195 Little Albany Street, New Brunswick, NJ 08903, USA
⁵ Center for Advanced Biotechnology and Medicine, Department of Molecular Biology and Biochemistry, Rutgers University, 679 Hoes Lane, Piscataway, NJ 08854, USA

^* Author for correspondence (e-mail: ewhite{at}cabm.rutgers.edu)

Accepted 17 October 2006

During tumorigenesis, normal growth mechanisms are deregulated and safeguards that eliminate abnormal cells by apoptosis are disabled. Tumor cells must also increase nutrient uptake and angiogenesis to support the upregulation of metabolism necessary for unrestricted growth. In addition, they have to rely on inefficient energy production by glycolysis. This glycolytic state can result from mutations that promote cell proliferation, the hypoxic tumor microenvironment and perhaps mitochondrial malfunction. Moreover, the very signals that enable unrestricted cell proliferation inhibit autophagy, which normally sustains cells during nutrient limitation. In tumors, inactivation of the autophagy pathway may enhance necrosis and inflammation and promote genomic instability, which can further enhance tumor growth. Thus, tumor cells cannot adapt efficiently to metabolic stress and could be induced to die by metabolic catastrophe, in which high energy demand is contrasted by insufficient energy production. Efforts to exploit this unique metabolic state clinically previously focused mainly on detecting tissue displaying increased glycolytic metabolism. The challenge now is to induce metabolic catastrophe therapeutically as an approach to killing the unkillable cells.

Key words: Autophagy, Apoptosis, AKT, mTOR, BCL-2, Beclin1, Cancer

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. Shanmugam, S. K. McBrayer, J. Qian, K. Raikoff, M. J. Avram, S. Singhal, V. Gandhi, P. T. Schumacker, N. L. Krett, and S. T. Rosen Targeting Glucose Consumption and Autophagy in Myeloma with the Novel Nucleoside Analogue 8-Aminoadenosine J. Biol. Chem., September 25, 2009; 284(39): 26816 - 26830. [Abstract] [Full Text] [PDF]

				E. White and R. S. DiPaola The Double-Edged Sword of Autophagy Modulation in Cancer Clin. Cancer Res., September 1, 2009; 15(17): 5308 - 5316. [Abstract] [Full Text] [PDF]

				S. B. Shears Diphosphoinositol Polyphosphates: Metabolic Messengers? Mol. Pharmacol., August 1, 2009; 76(2): 236 - 252. [Abstract] [Full Text] [PDF]

				S Ghavami, M Hashemi, S R Ande, B Yeganeh, W Xiao, M Eshraghi, C J Bus, K Kadkhoda, E Wiechec, A J Halayko, et al. Apoptosis and cancer: mutations within caspase genes J. Med. Genet., August 1, 2009; 46(8): 497 - 510. [Abstract] [Full Text] [PDF]

				S. Wilkinson, J. O'Prey, M. Fricker, and K. M. Ryan Hypoxia-selective macroautophagy and cell survival signaled by autocrine PDGFR activity Genes & Dev., June 1, 2009; 23(11): 1283 - 1288. [Abstract] [Full Text] [PDF]

				H. Wu, H. Zhu, D. X. Liu, T.-K. Niu, X. Ren, R. Patel, W. N. Hait, and J.-M. Yang Silencing of Elongation Factor-2 Kinase Potentiates the Effect of 2-Deoxy-D-Glucose against Human Glioma Cells through Blunting of Autophagy Cancer Res., March 15, 2009; 69(6): 2453 - 2460. [Abstract] [Full Text] [PDF]

				Y Sun and Z-L Peng Programmed cell death and cancer Postgrad. Med. J., March 1, 2009; 85(1001): 134 - 140. [Abstract] [Full Text] [PDF]

				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]

				J. M. Phang, J. Pandhare, and Y. Liu The Metabolism of Proline as Microenvironmental Stress Substrate J. Nutr., October 1, 2008; 138(10): 2008S - 2015S. [Abstract] [Full Text] [PDF]

				K. Singletary and J. Milner Diet, Autophagy, and Cancer: A Review Cancer Epidemiol. Biomarkers Prev., July 1, 2008; 17(7): 1596 - 1610. [Abstract] [Full Text] [PDF]

				E. White Autophagy and Apoptosis Modulation in Cancer Therapy Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 345 - 348. [Abstract] [Full Text] [PDF]

				C. Fung, R. Lock, S. Gao, E. Salas, and J. Debnath Induction of Autophagy during Extracellular Matrix Detachment Promotes Cell Survival Mol. Biol. Cell, March 1, 2008; 19(3): 797 - 806. [Abstract] [Full Text] [PDF]

				Y. Yamada, K. D. Davis, and C. R. Coffman Programmed cell death of primordial germ cells in Drosophila is regulated by p53 and the Outsiders monocarboxylate transporter Development, January 15, 2008; 135(2): 207 - 216. [Abstract] [Full Text] [PDF]