TY  - JOUR
A1  - Kosnopfel, Corinna
A1  - Sinnberg, Tobias
A1  - Sauer, Birgit
A1  - Niessner, Heike
A1  - Muenchow, Alina
A1  - Fehrenbacher, Birgit
A1  - Schaller, Martin
A1  - Mertens, Peter R.
A1  - Garbe, Claus
A1  - Thakur, Basant Kumar
A1  - Schittek, Birgit
T1  - Tumour progression stage-dependent secretion of YB-1 stimulates melanoma cell migration and invasion
JF  - Cancers
N2  - Secreted factors play an important role in intercellular communication. Therefore, they are not only indispensable for the regulation of various physiological processes but can also decisively advance the development and progression of tumours. In the context of inflammatory disease, Y-box binding protein 1 (YB-1) is actively secreted and the extracellular protein promotes cell proliferation and migration. In malignant melanoma, intracellular YB-1 expression increases during melanoma progression and represents an unfavourable prognostic marker. Here, we show active secretion of YB-1 from melanoma cells as opposed to benign cells of the skin. Intriguingly, YB-1 secretion correlates with the stage of melanoma progression and depends on a calcium- and ATP-dependent non-classical secretory pathway leading to the occurrence of YB-1 in the extracellular space as a free protein. Along with an elevated YB-1 secretion of melanoma cells in the metastatic growth phase, extracellular YB-1 exerts a stimulating effect on melanoma cell migration, invasion, and tumourigenicity. Collectively, these data suggest that secreted YB-1 plays a functional role in melanoma cell biology, stimulating metastasis, and may serve as a novel biomarker in malignant melanoma that reflects tumour aggressiveness.
KW  - melanoma
KW  - secretion
KW  - Y-box binding protein 1
KW  - migration and invasiveness
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211206
SN  - 2072-6694
VL  - 12
IS  - 8
ER  - 
TY  - JOUR
A1  - Glutsch, Valerie
A1  - Amaral, Teresa
A1  - Garbe, Claus
A1  - Thoms, Kai-Martin
A1  - Mohr, Peter
A1  - Hauschild, Axel
A1  - Schilling, Bastian
T1  - Indirect Comparison of Combined BRAF and MEK Inhibition in Melanoma Patients with Elevated Baseline Lactate Dehydrogenase
JF  - Acta Dermato-Venereologica
N2  - The approval of BRAF and MEK inhibitors has signifi-cantly improved treatment outcomes for patients with BRAF-mutated metastatic melanoma. The 3 first-line targeted therapy trials have provided similar results, and thus the identification of predictive biomarkers may generate a more precise basis for clinical deci-sion-making. Elevated baseline lactate dehydrogenase (LDH) has already been determined as a strong prog-nostic factor. Therefore, this indirect analysis compa-red subgroups with elevated baseline LDH across the pivotal targeted therapy trials co-BRIM, COMBI-v and COLUMBUS part 1. The Bucher method was used to compare progression-free survival, objective response rate and overall survival indirectly. The results show a non-significant risk reduction for progression in the subgroup with elevated baseline LDH receiving vemu-rafenib plus cobimetinib compared with dabrafenib plus trametinib and encorafenib plus binimetinib. Al-though an indirect comparison, these data might pro-vide some guidance for treatment recommendations in melanoma patients with elevated LDH.
KW  - melanoma
KW  - BRAF
KW  - lactate dehydrogenase
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230190
VL  - 100
ER  -