Characterization of UVA induced metabolic changes in melanoma in vitro and in vivo and identification of therapeutic targets
Final Report Abstract
Taken together, we could find new metabolic pathways which are changed upon UVA irradiation. Furthermore we unraveled metabolic changes upon UVA irradiation which are not limited to human melanoma cells and are also present in murine and human melanocytes, keratinocytes and fibroblasts. The UVA enhanced lactic acid production and secretion of these cells could promote progression of initial melanomas and contribute to UVA induced immune suppression. Many of the UVA induced metabolic changes seem to be involved in antioxidant defense of UVA induced ROS. In the scenario of UVA-induced glycolysis and pyruvate production the melanoma cells or fibroblasts, keratinocytes and melanocytes could use elevated pyruvate level as additional antioxidant. As pyruvate could be an important metabolite involved in UVA induced antioxidant defense, the interference with glycolysis seems to be an interesting target disturbing UVA induced melanoma metabolism. This is subject to ongoing research in our group. Further UVA-induced metabolic changes in human skin cells and murine skin and the role of pyruvate for ROS detoxification are subject to ongoing research.
Publications
- (2014) Genetic defects and ultraviolet radiation: from old virtues in the clinic to new scientific developments in rare diseases - and back. J Dtsch Dermatol Ges. Oct;12(10):841-2
Berneburg M.
(See online at https://doi.org/10.1111/ddg.12461) - (2014) Luminescent dual sensors reveal extracellular pH-gradients and hypoxia on chronic wounds that disrupt epidermal repair. Theranostics. Apr 30;4(7):721-35
Schreml S, Meier RJ, Kirschbaum M, Kong SC, Gehmert S, Felthaus O, Küchler S, Sharpe JR, Wöltje K, Weiß KT, Albert M, Seidl U, Schröder J, Morsczeck C, Prantl L, Duschl C, Pedersen SF, Gosau M, Berneburg M, Wolfbeis OS, Landthaler M, Babilas P
(See online at https://doi.org/10.7150/thno.9052) - (2015) Activating mutations in the RAS/mitogen-activated protein kinase signaling pathway in sporadic trichoblastoma and syringocystadenoma papilliferum. Hum Pathol. Feb;46(2):272-6
Shen AS, Peterhof E, Kind P, Rütten A, Zelger B, Landthaler M, Berneburg M, Hafner C, Groesser L
(See online at https://doi.org/10.1016/j.humpath.2014.11.002) - (2015) Glucose transporter isoform 1 expression enhances metastasis of malignant melanoma cells. Oncotarget. Oct 20;6(32):32748-60
Koch A, Lang SA, Wild PJ, Gantner S, Mahli A, Spanier G, Berneburg M, Müller M, Bosserhoff AK, Hellerbrand C
(See online at https://doi.org/10.18632/oncotarget.4977) - (2015) Quantitative proteomics of the human skin secretome reveal a reduction in immune defense mediators in ectodermal dysplasia patients. Invest Dermatol. Mar;135(3):759-767
Burian M, Velic A, Matic K, Günther S, Kraft B, Gonser L, Forchhammer S, Tiffert Y, Naumer C, Krohn M, Berneburg M, Yazdi AS, Maček B, Schittek B J
(See online at https://doi.org/10.1038/jid.2014.462) - (2016) LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells.Cell Metab. Nov 8;24(5):657-671
Brand A, Singer K, Koehl GE, Kolitzus M, Schoenhammer G, Thiel A, Matos C, Bruss C, Klobuch S, Peter K, Kastenberger M, Bogdan C, Schleicher U, Mackensen A, Ullrich E, Fichtner-Feigl S, Kesselring R, Mack M, Ritter U, Schmid M, Blank C, Dettmer K, Oefner PJ, Hoffmann P, Walenta S, Geissler EK, Pouyssegur J, Villunger A, Steven A, Seliger B, Schreml S, Haferkamp S, Kohl E, Karrer S, Berneburg M, Herr W, Mueller-Klieser W, Renner K, Kreutz M
(See online at https://doi.org/10.1016/j.cmet.2016.08.011) - (2016) Which melanoma patient carries a BRAF-mutation? A comparison of predictive models. Oncotarget. Jun 14;7(24):36130-36137
Eigentler T, Assi Z, Hassel JC, Heinzerling L, Starz H, Berneburg M, Bauer J, Garbe C
(See online at https://doi.org/10.18632/oncotarget.9143) - (2016). UVA-Irradiation Induces Melanoma Invasion via the Enhanced Warburg Effect J Invest Dermatol. Sep;136(9):1866-1875
Kamenisch Y, Baban TSA, Schuller W, von Thaler AK, Sinnberg T, Metzler G, Bauer J, Schittek B, Garbe C, Rocken M, Berneburg M
(See online at https://doi.org/10.1016/j.jid.2016.02.815) - (2018) UVA, metabolism and melanoma: UVA makes melanoma hungry for metastasis. Exp Dermatol. Sep;27(9):941-949
Kamenisch Y, Ivanova I, Drexler K, Berneburg M
(See online at https://doi.org/10.1111/exd.13561)
