Characterization of glycolysis-related gene expression in malignant melanoma

Koch A, Ebert EV, Seitz T, Dietrich P, Berneburg M, Boßerhoff AK, Hellerbrand C (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Pathology Research and Practice Elsevier

Book Volume: 216

Article Number: 152752

Journal Issue: 1

DOI: 10.1016/j.prp.2019.152752

Abstract

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.

Authors with CRIS profile

Andreas Koch Lehrstuhl für Biochemie und Molekulare Medizin Tatjana Seitz Professur für Biochemie und Molekulare Pathobiologie Peter Dietrich Lehrstuhl für Biochemie und Molekulare Medizin Anja Katrin Boßerhoff Lehrstuhl für Biochemie und Molekulare Medizin Claus Hellerbrand Professur für Biochemie und Molekulare Pathobiologie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

D032: The role of neuropeptide Y in chemo-resistance and immune checkpoint inhibition in hepatocellular carcinoma March 1, 2020 - Feb. 28, 2023

Involved external institutions

Universitätsklinikum Regensburg DE Germany (DE)

How to cite

APA:

Koch, A., Ebert, E.V., Seitz, T., Dietrich, P., Berneburg, M., Boßerhoff, A.K., & Hellerbrand, C. (2020). Characterization of glycolysis-related gene expression in malignant melanoma. Pathology Research and Practice, 216(1). https://doi.org/10.1016/j.prp.2019.152752

MLA:

Koch, Andreas, et al. "Characterization of glycolysis-related gene expression in malignant melanoma." Pathology Research and Practice 216.1 (2020).

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