Glioma stem-like cells evade interferon suppression through MBD3/NuRD complex–mediated STAT1 downregulation

• DOI: 10.1084/jem.20191340
• Publication Date: 2020-03-17T13:20:31Z
• Authors: Xiaoyan Zhan; Saisai Guo; Yuanyuan Li; Haowen Ran; Haohao Huang; Lanjuan Mi; Jin Wu; Xinzheng Wang; Dake Xiao; Lishu Chen; Da Li; Songyang Zhang; Xu Yan; Yu Yu; Tingting Li; Qiuying Han; Kun He; Jiuwei Cui; Tao Li; Tao Zhou; Jeremy N. Rich; Shideng Bao; Xuemin Zhang; Ailing Li; Jianghong Man
• Keywords: STAT1

Type I interferons (IFNs) are known to mediate antineoplastic effects during tumor progression. IFNs can be produced by multiple cell types in the microenvironment; however, molecular mechanisms which cells evade inhibition of immune microenvironment remain unknown. Here we demonstrate that glioma stem-like (GSCs) type IFN suppression through downregulation STAT1 initiate growth under inhospitable conditions. The is mediated MBD3, an epigenetic regulator. MBD3 preferentially expressed GSCs and recruits NuRD complex promoter suppress expression histone deacetylation. Importantly, overexpression or depletion induces p21 transcription, resensitizes suppression, attenuates GSC growth, prolongs animal survival. Our findings inactivation signaling MBD3/NuRD provides with a survival advantage escape suggesting targeting may represent promising therapeutic opportunity compromise tumorigenic potential.