|タイトル:||Cystine uptake through the cystine/glutamate antiporter xCT triggers glioblastoma cell death under glucose deprivation|
|キーワード:||amino acid transport|
reactive oxygen species (ROS)
|出版者:||American Society for Biochemistry and Molecular Biolog (ASBMB)|
|誌名:||Journal of Biological Chemistry|
|抄録:||Oncogenic signaling in cancer cells alters glucose uptake and utilization to supply sufficient energy and biosynthetic intermediates for survival and sustained proliferation. Oncogenic signaling also prevents oxidative stress and cell death caused by increased production of reactive oxygen species. However, elevated glucose metabolism in cancer cells, especially in glioblastoma, results in the cells becoming sensitive to glucose deprivation (i.e. in high glucose dependence), which rapidly induces cell death. However, the precise mechanism of this type of cell death remains unknown. Here, we report that glucose deprivation alone does not trigger glioblastoma cell death. We found that, for cell death to occur in glucose-deprived glioblastoma cells, cystine and glutamine also need to be present in culture media. We observed that cystine uptake through the cystine/glutamate antiporter xCT under glucose deprivation rapidly induces NADPH depletion, reactive oxygen species accumulation, and cell death. We conclude that although cystine uptake is crucial for production of antioxidant glutathione in cancer cells its transport through xCT also induces oxidative stress and cell death in glucose-deprived glioblastoma cells. Combining inhibitors targeting cancer-specific glucose metabolism with cystine and glutamine treatment may offer a therapeutic approach for glioblastoma tumors exhibiting high xCT expression.|
|著作権等:||This research was originally published in the Journal of Biological Chemistry. [Takeo Goji, Kazuhiko Takahara, Manabu Negishi, Hironori Katoh.Cystine uptake through the cystine/glutamate antiporter xCT triggers glioblastoma cell death under glucose deprivation. J. Biol. Chem. 2017; 292:19721-19732]. © the American Society for Biochemistry and Molecular Biology.|
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