The role of thioredoxin reductase 1 in melanoma metabolism and metastasis |
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| Authors: | Robyn L. Poerschke Karen White Scott R. Florell Robert H. I. Andtbacka Joycelyn Tross Madeleine Anderson Sancy A. Leachman Philip J. Moos |
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| Affiliation: | 1. Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA;2. Department of Dermatology, University of Utah, Salt Lake City, UT, USA;3. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA;4. Department of Dermatology, Oregon Health & Science University, Portland, OH, USA |
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| Abstract: | Although significant progress has been made in targeted and immunologic therapeutics for melanoma, many tumors fail to respond, and most eventually progress when treated with the most efficacious targeted combination therapies thus far identified. Therefore, alternative approaches that exploit distinct melanoma phenotypes are necessary to develop new approaches for therapeutic intervention. Tissue microarrays containing human nevi and melanomas were used to evaluate levels of the antioxidant protein thioredoxin reductase 1 (TR1), which was found to increase as a function of disease progression. Melanoma cell lines revealed metabolic differences that correlated with TR1 levels. We used this new insight to design a model treatment strategy that creates a synthetic lethal interaction wherein targeting TR1 sensitizes melanoma to inhibition of glycolytic metabolism, resulting in a decrease in metastases in vivo. This approach holds the promise of a new clinical therapeutic strategy, distinct from oncoprotein inhibition. |
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| Keywords: | thioredoxinreductase melanoma immunohistochemistry metabolism mitochondria |
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