The role of thioredoxin reductase 1 in melanoma metabolism and metastasis

Pamela B. Cassidy, Matthew Honeggar, Robyn L. Poerschke, Karen White, Scott R. Florell, Robert H.I. Andtbacka, Joycelyn Tross, Madeleine Anderson, Sancy A. Leachman, Philip J. Moos

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)685-695
Number of pages11
JournalPigment Cell and Melanoma Research
Volume28
Issue number6
DOIs
StatePublished - Nov 2015

Keywords

  • Immunohistochemistry
  • Melanoma
  • Metabolism
  • Mitochondria
  • Thioredoxinreductase

ASJC Scopus subject areas

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology

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  • Cite this

    Cassidy, P. B., Honeggar, M., Poerschke, R. L., White, K., Florell, S. R., Andtbacka, R. H. I., Tross, J., Anderson, M., Leachman, S. A., & Moos, P. J. (2015). The role of thioredoxin reductase 1 in melanoma metabolism and metastasis. Pigment Cell and Melanoma Research, 28(6), 685-695. https://doi.org/10.1111/pcmr.12398