Epigenetic Regulation of Glucose Transporters in Non-Small Cell Lung Cancer
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 as...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2011-03-01
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| Series: | Cancers |
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| Online Access: | http://www.mdpi.com/2072-6694/3/2/1550/ |
| _version_ | 1797718633726607360 |
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| author | Steven G. Gray Calen Sacevich Lisa Kilmartin Jennifer Leonard Anne-Marie Baird Kenneth J. O'Byrne |
| author_facet | Steven G. Gray Calen Sacevich Lisa Kilmartin Jennifer Leonard Anne-Marie Baird Kenneth J. O'Byrne |
| author_sort | Steven G. Gray |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T08:54:12Z |
| format | Article |
| id | doaj.art-c2492b9c30344153b2ca34d6c39ae8b9 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T08:54:12Z |
| publishDate | 2011-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c2492b9c30344153b2ca34d6c39ae8b92023-09-02T16:12:15ZengMDPI AGCancers2072-66942011-03-01321550156510.3390/cancers3021550Epigenetic Regulation of Glucose Transporters in Non-Small Cell Lung CancerSteven G. GrayCalen SacevichLisa KilmartinJennifer LeonardAnne-Marie BairdKenneth J. O'ByrneDue 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.http://www.mdpi.com/2072-6694/3/2/1550/NSCLCGlucose transporterepigenetics |
| spellingShingle | Steven G. Gray Calen Sacevich Lisa Kilmartin Jennifer Leonard Anne-Marie Baird Kenneth J. O'Byrne Epigenetic Regulation of Glucose Transporters in Non-Small Cell Lung Cancer Cancers NSCLC Glucose transporter epigenetics |
| title | Epigenetic Regulation of Glucose Transporters in Non-Small Cell Lung Cancer |
| title_full | Epigenetic Regulation of Glucose Transporters in Non-Small Cell Lung Cancer |
| title_fullStr | Epigenetic Regulation of Glucose Transporters in Non-Small Cell Lung Cancer |
| title_full_unstemmed | Epigenetic Regulation of Glucose Transporters in Non-Small Cell Lung Cancer |
| title_short | Epigenetic Regulation of Glucose Transporters in Non-Small Cell Lung Cancer |
| title_sort | epigenetic regulation of glucose transporters in non small cell lung cancer |
| topic | NSCLC Glucose transporter epigenetics |
| url | http://www.mdpi.com/2072-6694/3/2/1550/ |
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