UVA-Irradiation Induces Melanoma Invasion via the Enhanced Warburg Effect

Kamenisch, York and Baban, Tarza S. A. and Schuller, Winfried and von Thaler, Anna-Katharina and Sinnberg, Tobias and Metzler, Gisela and Bauer, Juergen and Schittek, Birgit and Garbe, Claus and Rocken, Martin and Berneburg, Mark (2016) UVA-Irradiation Induces Melanoma Invasion via the Enhanced Warburg Effect. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 136 (9). pp. 1866-1875. ISSN 0022-202X, 1523-1747

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Abstract

Melanoma is a malignant tumor in which UVA (320-400 nm) radiation is considered to be an important risk factor. But the role of UVA in melanoma progression toward an invasive phenotype is still not adequately investigated. For most proliferating tumor cells the preference of aerobic glycolysis has been described as the Warburg effect. Here we investigate the effect of UVA irradiation on changes in the Warburg effect and tumor progression toward invasive potential. On UVA irradiation, melanoma cell lines from initial tumors show an induction of the Warburg effect with increased glucose consumption and lactate production, which is at least partially mediated by reactive oxygen species. Associated with UVA treatment and enhanced lactic acid production, tumor-relevant proteases and in situ invasion is upregulated. Simultaneously, UVA increases intracellular concentrations of progression marker transketolase and activated protein kinase Akt, both involved in metabolic changes that increase with proliferation. Using invasion assays we show that lactic acid, resulting from the UVA enhanced and partially reactive oxygen species-mediated Warburg effect, increases the invasive potential of all melanoma cell lines investigated. Therefore, we demonstrate in melanoma cells that production of lactic acid, induced by UVA irradiation, increases invasiveness of melanoma cells via expression of tumor-relevant proteases.

Item Type: Article
Uncontrolled Keywords: CUTANEOUS MALIGNANT-MELANOMA; ULTRAVIOLET-RADIATION; LACTIC-ACID; MATRIX METALLOPROTEINASE-3; CELL INVASION; IN-VIVO; EXPRESSION; METASTASIS; ACTIVATION; PROMOTES;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Dermatologie und Venerologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 04 Apr 2019 13:03
Last Modified: 04 Apr 2019 13:03
URI: https://pred.uni-regensburg.de/id/eprint/3416

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