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- W3112133090 abstract "Abstract Activation of mTORC1 plays a significant role in cancer development and progression. However, the metabolic mechanisms to sustain mTORC1 activation in stressed cancer cells are still underappreciated. Autophagy, one downstream process of mTORC1, is proposed to be suppressed under the condition of mTORC1 hyper-activation. Interestingly, we recently revealed higher autophagy activity in various Tsc-deficient tumor cells with mTORC1 hyper-activity. Nevertheless, the functions and mechanisms of autophagy in regulating mTORC1 in cancer cells are not well understood. In this study, we revealed a strong association of altered mRNA levels in mTORC1 upstream and downstream genes with poor prognosis of glioma patients. Our metabolic and molecular studies indicated that autophagy mediated lipid catabolism was essential to sustain mTORC1 activity in glioma cells under energy stresses. We found that autophagy inhibitors or fatty acid oxidation (FAO) inhibition in combination with 2-Deoxy-D-glucose (2DG) decreased oxidative phosphorylation, ATP production, mTORC1 activity, and survival of glioma cells in vitro. Consistently, the combination of chloroquine (CQ) or FAO inhibitors with 2DG effectively suppressed the progression of xenografted glioma with mTORC1 hyperactivation in mice. This study established a novel autophagy/lipid degradation/FAO/ATP pathway that maintains high mTORC1 signaling and tumor progression in brain cancer cells under energy stresses. The requirement of lipophagy in brain cancers may provide an opportunity to develop new molecular therapeutic targets to counteract mTORC1 for tumor progression." @default.
- W3112133090 created "2020-12-21" @default.
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- W3112133090 date "2020-11-01" @default.
- W3112133090 modified "2023-09-27" @default.
- W3112133090 title "TAMI-35. AUTOPHAGY MEDIATED LIPID CATABOLISM FACILITATES GLIOMA PROGRESSION TO OVERCOME BIOENERGETIC CRISIS" @default.
- W3112133090 doi "https://doi.org/10.1093/neuonc/noaa215.923" @default.
- W3112133090 hasPublicationYear "2020" @default.
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