Debra Mayes (Advisor), Robert Putnam (Committee Member), Christopher Wyatt (Committee Member)
Master of Science (MS)
Malignant transformation is the process by which cells develop cancer properties. While many causes for malignant transformation are known (i.e. common genetic mutations and/or exposure to toxins or viruses), the basic requirements that allow a cell to stay alive with altered nutrient and energy requirements are just now being studied. In some tumor types malignant cells undergo changes that result in metabolic differences compared to normal cells. These can include defects in mitophagy resulting in an accumulation of dysfunctional mitochondria and/or a metabolic switch resulting in increased glycolysis, termed the Warburg effect. Increased tumor growth and metastasis have also been associated with mitochondrial DNA mutations in some tumor types. In this study, we characterized the mitochondrial function of malignant peripheral nerve sheath tumor (MPNST) cell lines commonly used to study malignant transformation in Neurofibromatosis Type I. We identified metabolic differences between NF1-wildtype (STS26T) and NF1-deficient (ST88-14, 90-8, and S462) MPNST cell lines by measuring extracellular acidification and oxygen consumption, mitochondrial respiration protein expression, and ROS levels. Similar to findings from other malignant tumors, all MPNST cell lines were more glycolytic compared to non-tumorigenic normal human Schwann cells and surprisingly NF1-deficiency correlated with lower glycolytic and mitochondrial respiratory rate compared to wildtype MPNST. Mitochondrial respiratory rates and respiratory protein expression were significantly lower in the NF1-deficient MPNST cell lines when compared to NF1-wildtype MPNST cells. These findings demonstrate that neurofibromin affects glycolysis and mitochondrial respiration in malignant cells.
Department or Program
Department of Neuroscience, Cell Biology, and Physiology
Year Degree Awarded
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