Epigenetic regulation of glucose transporters in non-small cell lung cancer
O'Byrne, Kenneth J., Baird, Anne-Marie, Kilmartin, Lisa, Leonard, Jennifer, Sacevich, Calen, & Gray , Steven G. (2011) Epigenetic regulation of glucose transporters in non-small cell lung cancer. Cancers, 3(2), pp. 1550-1565.
Due to their inherently hypoxic environment, cancer cells often resort to glycolysis, or the anaerobic breakdown of glucose to form ATP to provide for their energy needs, known as the Warburg effect. At the same time, overexpression of the insulin receptor in non-small cell lung cancer (NSCLC) is associated with an increased risk of metastasis and decreased survival. The uptake of glucose into cells is carried out via glucose transporters or GLUTs. Of these, GLUT-4 is essential for insulin-stimulated glucose uptake. Following treatment with the epigenetic targeting agents histone deacetylase inhibitors (HDACi), GLUT-3 and GLUT-4 expression were found to be induced in NSCLC cell lines, with minimal responses in transformed normal human bronchial epithelial cells (HBECs). Similar results for GLUT-4 were observed in cells derived from liver, muscle, kidney and pre-adipocytes. Bioinformatic analysis of the promoter for GLUT-4 indicates that it may also be regulated by several chromatin binding factors or complexes including CTCF, SP1 and SMYD3. Chromatin immunoprecipitation studies demonstrate that the promoter for GLUT-4 is dynamically remodeled in response to HDACi. Overall, these results may have value within the clinical setting as (a) it may be possible to use this to enhance fluorodeoxyglucose (18F) positron emission tomography (FDG-PET) imaging sensitivity; (b) it may be possible to target NSCLC through the use of HDACi and insulin mediated uptake of the metabolic targeting drugs such as 2-deoxyglucose (2-DG); or (c) enhance or sensitize NSCLC to chemotherapy. © 2011 by the authors; licensee MDPI, Basel, Switzerland.
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|Item Type:||Journal Article|
|Keywords:||Epigenetics, Glucose transporter, NSCLC, 4 phenylbutyric acid, 5 aza 2' deoxycytidine, adenosine triphosphate, deoxyglucose, fluorodeoxyglucose f 18, glucose, glucose transporter 3, glucose transporter 4, histone deacetylase inhibitor, histone lysine methyltransferase, insulin, insulin receptor, messenger RNA, pregnancy specific beta1 glycoprotein, transcription factor CTCF, tributyrate, trichostatin A, unclassified drug, vorinostat, article, bioinformatics, bronchus mucosa, cancer cell, cancer cell culture, cancer survival, cell hypoxia, cell transformation, chemosensitivity, chromatin assembly and disassembly, chromatin immunoprecipitation, controlled study, drug targeting, energy consumption, epithelium cell, genetic regulation, glucose transport, glycolysis, histone acetylation, human, human cell, kidney cell, liver cell, lung non small cell cancer, metastasis potential, muscle cell, positron emission tomography, proadipocyte, promoter region, protein expression, sensitivity and specificity|
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2011 M D P I AG|
|Deposited On:||10 Dec 2013 02:18|
|Last Modified:||29 Jul 2014 23:38|
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