دورية أكاديمية
Targeting Glioblastoma Stem Cells with 2-Deoxy-D-Glucose (2-DG) Potentiates Radiation-Induced Unfolded Protein Response (UPR).
| العنوان: | Targeting Glioblastoma Stem Cells with 2-Deoxy-D-Glucose (2-DG) Potentiates Radiation-Induced Unfolded Protein Response (UPR). |
|---|---|
| المؤلفون: | Shah, Sumedh S., Rodriguez, Gregor A., Musick, Alexis, Walters, Winston M., de Cordoba, Nicolas, Barbarite, Eric, Marlow, Megan M., Marples, Brian, Prince, Jeffrey S., Komotar, Ricardo J., Vanni, Steven, Graham, Regina M. |
| المصدر: | Cancers; Feb2019, Vol. 11 Issue 2, p159, 1p |
| مصطلحات موضوعية: | STEM cells, AUTOPHAGY, APOPTOSIS, CELL lines, CELLULAR signal transduction, DOSE-effect relationship in pharmacology, ELECTRON microscopy, ENDOPLASMIC reticulum, GENE expression, GLIOMAS, GLUCOSE, DOSE-response relationship (Radiation), NEUROGLIA, PROTEINS, WESTERN immunoblotting, PHYSIOLOGY |
| مستخلص: | Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, and despite optimized treatment options, median survival remains dismal. Contemporary evidence suggests disease recurrence results from expansion of a robustly radioresistant subset of GBM progenitor cells, termed GBM stem cells (GSCs). In this study, we utilized transmission electron microscopy to uncover ultrastructural effects on patient-derived GSC lines exposed to supratherapeutic radiotherapy levels. Elevated autophagosome formation and increased endoplasmic reticulum (ER) internal diameter, a surrogate for ER stress and activation of unfolded protein response (UPR), was uncovered. These observations were confirmed via protein expression through Western blot. Upon interrogating genomic data from an open-access GBM patient database, overexpression of UPR-related chaperone protein genes was inversely correlated with patient survival. This indicated controlled UPR may play a role in promoting radioresistance. To determine if potentiating UPR further can induce apoptosis, we exposed GSCs to radiation with an ER stress-inducing drug, 2-deoxy-D-glucose (2-DG), and found dose-dependent decreases in viability and increased apoptotic marker expression. Taken together, our results indicate GSC radioresistance is, in part, achieved by overexpression and overactivation of ER stress-related pathways, and this effect can be overcome via potentiation of UPR, leading to loss of GSC viability. [ABSTRACT FROM AUTHOR] |
| Copyright of Cancers is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| قاعدة البيانات: | Complementary Index |
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