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Table of Contents
Vol. 53, No. 4, 2007
Issue release date: July 2007
Section title: Pharmacology
Chemotherapy 2007;53:233–256
(DOI:10.1159/000104457)

Hypoxic Regulation of Glucose Transport, Anaerobic Metabolism and Angiogenesis in Cancer: Novel Pathways and Targets for Anticancer Therapeutics

Airley R.E. · Mobasheri A.
aDepartment of Developmental and Molecular Biology, Chanin Institute, Albert Einstein College of Medicine of Yeshiva University, Bronx, N.Y., USA; bMolecular Pathogenesis Research Group, Department of Veterinary Preclinical Sciences, University of Liverpool, Liverpool, and Division of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK

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Article / Publication Details

First-Page Preview
Abstract of Pharmacology

Received: 10/11/2005
Accepted: 5/9/2006
Published online: 6/25/2007

Number of Print Pages: 24
Number of Figures: 9
Number of Tables: 1

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

For additional information: http://www.karger.com/CHE

Abstract

Cancer cells require a steady source of metabolic energy in order to continue their uncontrolled growth and proliferation. Accelerated glycolysis is one of the biochemical characteristics of cancer cells. Recent work indicates that glucose transport and metabolism are essential for the posttreatment survival of tumor cells, leading to poor prognosis. Glycolytic breakdown of glucose is preceded by the transport of glucose across the cell membrane, a rate-limiting process mediated by facilitative glucose transporter proteins belonging to the facilitative glucose transporter/solute carrier GLUT/SLC2A family. Tumors frequently show overexpression of GLUTs, especially the hypoxia-responsive GLUT1 and GLUT3 proteins. There are also studies that have reported associations between GLUT expression and proliferative indices, whilst others suggest that GLUT expression may be of prognostic significance. In this article we revisit Warburg’s original hypothesis and review the recent clinical and basic research on the expression of GLUT family members in human cancers and in cell lines derived from human tumors. We also explore the links between hypoxia-induced genes, glucose transporters and angiogenic factors. Hypoxic tumors are significantly more malignant, metastatic, radio- and chemoresistant and have a poor prognosis. With the discovery the oxygen-sensitive transcription factor hypoxia-inducible factor (HIF-1) has come a new understanding of the molecular link between hypoxia and deregulated glucose metabolism. HIF-1 induces a number of genes integral to angiogenesis, e.g. vascular endothelial growth factor (VEGF), a process intimately involved with metastatic spread. This knowledge may enhance existing chemotherapeutic strategies so that treatment can be more rationally applied and personalized for cancer patients.


  

Author Contacts

Ali Mobasheri, BSc (Hons), ARCS, MSc, DPhil (Oxon)
Associate Professor and Reader in Comparative Physiology
Division of Veterinary Medicine, School of Veterinary Medicine and Science
University of Nottingham, Sutton Bonington Campus, Leicestershire LE12 5RD (UK)
Tel. +44 115 951 6449, Fax +44 115 951 6415, E-Mail ali.mobasheri@nottingham.ac.uk

  

Article Information

Received: October 11, 2005
Accepted after revision: May 9, 2006
Published online: June 25, 2007
Number of Print Pages : 24
Number of Figures : 9, Number of Tables : 1, Number of References : 220

  

Publication Details

Chemotherapy (International Journal of Experimental and Clinical Chemotherapy)

Vol. 53, No. 4, Year 2007 (Cover Date: July 2007)

Journal Editor: Sörgel, F. (Nürnberg-Heroldsberg)
ISSN: 0009–3157 (print), 1421–9794 (Online)

For additional information: http://www.karger.com/CHE


Article / Publication Details

First-Page Preview
Abstract of Pharmacology

Received: 10/11/2005
Accepted: 5/9/2006
Published online: 6/25/2007

Number of Print Pages: 24
Number of Figures: 9
Number of Tables: 1

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

For additional information: http://www.karger.com/CHE


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