Abstract 1145: The TDP-43 confers resistance to metabolic stress condition via activating autophagy in GBM cells

Abstract

Abstract Glioblastoma (GBM) is the most aggressive malignant brain tumor in adults. TDP-43 (TARDBP), a DNA and RNA binding protein, is well known to play a key role in RNA processing, including involving in the pathogenesis of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Recent reports suggested that TDP-43 participate to the regulation of metabolic glycolysis in cancer. Overcoming metabolic stress is critical for cancer cell survival and growth in nutrient deprivation condition. Herein we found protein level of TDP-43 was increased in nutrient deprivation. Overexpression TDP-43 promotes glioblastoma cell survival and suppressed the activated-form levels of caspase 3 protein under nutrient deprivation. Overexpression of TDP-43 increased the tumorigenicity as determined by anchorage-independent growth assay and xenografts in immunocompromised mice model. Under nutrient deprivation, we also found that TDP-43-overexpression induced autophagy. Recent evidence suggests that autophagy is a cell survival mechanism in cancer cells. Finally, treatment of autophagy inhibitor blocks the survival of TDP-43 overexpressing GBM cells in nutrient deprivation condition. By this study, we presume TDP-43 enhanced GBM cells tumorigincity, activated autophagy and inhibited cell death under nutrient deprivation condition. TDP-43 is potentially the new aspects for understanding the tumorigenicity and metablolic regulation for malignant brain tumors and GBM. Citation Format: Tzu-Wei Lin, Chen-Wen Wu. The TDP-43 confers resistance to metabolic stress condition via activating autophagy in GBM cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1145. doi:10.1158/1538-7445.AM2015-1145