Exploring the role of Cytoglobin (CYGB) in melanoma pathobiology
by Julian Wojtachnia
Date of Examination:2025-02-17
Date of issue:2025-01-17
Advisor:Dr. Ivan Prof Bogeski
Referee:Prof. Dr. Frauke Alves
Referee:Prof. Dr. Dieter Kube
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Abstract
English
Skin cancer is one of the most common malignancies worldwide, with melanoma being the deadliest form. Although both targeted therapies inhibiting the MAPK pathway and immunotherapy have improved the prognosis of patients significantly, disease relapse resulting from drug resistance is still the major challenge in melanoma treatment. Therefore, the identification and functional classification of new therapeutic targets in melanoma is essential. In this study, we identified Cytoglobin (CYGB), a protein from the globin family which is commonly downregulated during melanocyte malignant transformation, as a potential therapeutic target for melanoma treatment. We characterized the role of CYGB in melanoma by inducing CYGB knock-down in three different melanoma cell lines. Our results indicate that upon CYGB depletion melanoma cells display decreased colony formation, diminished global translation and increased susceptibility to the thioredoxin reductase (TRXR) inhibitor Auranofin. However, CYGB expression had no effect on the efficacy pf BRAF and MEK inhibitors Vemurafenib and Trametinib as well as NK cell- mediated cytotoxicity. Taken together, our findings indicate that CYGB controls melanoma cell metabolic state as well as melanoma cell phenotype. Further studies are warranted in elucidating the therapeutic potential of CYGB in melanoma and other cancer entities.
Keywords: melanoma; Cytoglobin
Schlagwörter: melanoma; Cytoglobin