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Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: novel pathways and targets for anticancer therapeutics.

Airley, RE and Mobasheri, A (2007) Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: novel pathways and targets for anticancer therapeutics. Chemotherapy, 53 (4). pp. 233-256.

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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.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Airley, RE
Date : 2007
DOI : 10.1159/000104457
Uncontrolled Keywords : Anaerobiosis, Animals, Anoxia, Biological Transport, Fluorodeoxyglucose F18, Glucose, Glucose Transport Proteins, Facilitative, Glucose Transporter Type 1, Glucose Transporter Type 3, Glycolysis, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Neoplasms, Neovascularization, Pathologic, Positron-Emission Tomography
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:12
Last Modified : 24 Jan 2020 18:42

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