GLS-driven glutamine catabolism contributes to prostate cancer radiosensitivity by regulating the redox state, stemness and ATG5-mediated autophagy
Anna Mukha, Uğur Kahya, Annett Linge, Oleg Chen, Steffen Löck, Vasyl Lukiyanchuk, Susan Richter, Tiago C. Alves, Mirko Peitzsch, Vladyslav Telychko, Sergej Skvortsov, Giulia Negro, Bertram Aschenbrenner, Ira Skvortsova, Peter Mirtschink, Fabian Lohaus, Tobias Hölscher, Hans Neubauer, Mahdi Rivandi, Vera Labitzky, Tobias Lange, André Franken, Bianca Behrens, Nikolas H. Stoecklein, Marieta Toma, Ulrich Sommer, Sebastian Zschaeck, Maximilian Rehm, Graeme Eisenhofer, Christian Schwager, Amir Abdollahi, Christer Groeben, Leoni A. Kunz‐Schughart, Gustavo Baretton, Michaël Baumann, Mechthild Krause, Claudia Peitzsch, Anna Dubrovska
Abstract
Radiotherapy is one of the curative treatment options for localized prostate cancer (PCa). The curative potential of radiotherapy is mediated by irradiation-induced oxidative stress and DNA damage in tumor cells. However, PCa radiocurability can be impeded by tumor resistance mechanisms and normal tissue toxicity. Metabolic reprogramming is one of the major hallmarks of tumor progression and therapy resistance. Specific metabolic features of PCa might serve as therapeutic targets for tumor radiosensitization and as biomarkers for