Lishu Chen, Qinghui Qi, Xiaoqing Jiang, Jin Wu, Yuanyuan Li, Zhaodan Liu, Yan Cai, Haowen Ran, Songyang Zhang, Cheng Zhang, Huiran Wu, Shuailiang Cao, Lanjuan Mi, Dake Xiao, Haohao Huang, Shuai Jiang, Jiaqi Wu, Bohan Li, Jiong Xie, Ji Qi, Fangye Li, Panpan Liang, Qiuying Han, Min Wu, Wenchao Zhou, Chenhui Wang, Weina Zhang, Xin Jiang, Kun Zhang, Huiyan Li, Xuemin Zhang, Ailing Li, Tao Zhou, Jianghong Man
Glioblastoma (GBM) exhibits profound metabolic plasticity for survival and therapeutic resistance, while the underlying mechanisms remain unclear. Here, we show that GBM stem cells (GSCs) reprogram the epigenetic landscape by producing substantial amounts of phosphocreatine (PCr). This production is attributed to the elevated transcription of brain-type creatine kinase (CKB), mediated by Zinc finger E-box binding homeobox 1 (ZEB1). PCr inhibits the poly-ubiquitination of the chromatin regulator bromodomain containing protein 2 (BRD2) by outcompeting the E3 ubiquitin ligase SPOP for BRD2 binding...
April 2, 2024: Cancer Discovery