Koch, Andreas and Ebert, Eva Vanessa and Seitz, Tatjana and Dietrich, Peter and Berneburg, Mark and Bosserhoff, Anja and Hellerbrand, Claus (2020) Characterization of glycolysis-related gene expression in malignant melanoma. PATHOLOGY RESEARCH AND PRACTICE, 216 (1): 152752. ISSN 0344-0338,
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Malignant melanoma exhibits a distinct metabolic phenotype with high glycolytic activity. Previously, we have shown that glucose transporter isoform 1 (GLUT1) favors growth and metastasis of malignant melanoma. In this study, we investigated the expression of GLUT1 and the further glycolysis-related genes hexokinase 1 and 2 (HK1, HK2), lactate dehydrogenase A (LDH-A) and monocarboxylate transporters 1 and 4 (MCT1, MCT4) in eleven human melanoma cell lines under normoxic and hypoxic conditions. Furthermore, a set of 25 human malignant melanoma tissue samples was analyzed. Under hypoxic conditions, we could observe a significant upregulation of hypoxia-inducible factor 1 alpha (HIF-1a) target genes GLUT1, HK2 and LDH-A, but not MCT4. While under normoxic conditions the expression of glycolysis-related genes showed no correlation with origin or BRAF mutation status, GLUT1 expression was significantly elevated in metastatic and BRAF-V600E mutated melanoma cell lines under hypoxic conditions. Furthermore, GLUT1 expression in human melanoma tissue samples correlated significantly with HK1, LDH-A and MCT1 expression, confirming a glycolytic phenotype. Notably, Cyclin D1 expression, which is used as a prognostic marker for the outcome of melanoma patients, as it is associated with proliferation and invasiveness of melanoma, significantly correlated with GLUT1, HK1, LDH-A and MCT1 expression. In summary, our findings provide further evidence that enhanced glycolytic activity in melanoma favors disease progression and is an attractive therapeutic target for this highly aggressive tumor.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CELL-LINES; IN-VITRO; METABOLISM; HYPOXIA; LACTATE; ANTIBODIES; TUMORS; MCT1; GLUT1; Glycolysis; Melanoma; HK1; HK2; MCT1; MCT4; LDH-A; Cyclin D1 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Apr 2021 08:35 |
| Last Modified: | 07 Apr 2021 08:35 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45489 |
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