Epigenetic and molecular coordination between HDAC2 and SMAD3-SKI regulates essential brain tumour stem cell characteristics

Abstract Histone deacetylases are important epigenetic regulators that have been reported to play essential roles in cancer stem cell functions and promising therapeutic targets many cancers including glioblastoma. However, the functionally relevant of specific histone deacetylases, maintenance key self-renewal growth characteristics brain tumour (BTSC) sub-populations glioblastoma, remain be fully resolved. Here, using pharmacological inhibition genetic loss gain function approaches, we identify HDAC2 as most deacetylase for re-organization chromatin accessibility resulting BTSC properties. Furthermore, its interaction with transforming factor-β pathway related proteins, SMAD3 SKI, is crucial tumorigenic potential BTSCs vitro orthotopic xenograft models. Inhibition activity disruption coordinated mechanisms regulated by HDAC2-SMAD3-SKI axis thus approaches targeting BTSCs.