Abstract
Glioma stem-like cells (GSCs) comprise the critical subpopulation with the properties of self-renewal and tumorigenesis. Striking parallels between cancer stem-like cells (CSCs) and normal stem cells indicate that tumor cells may evolve from CSCs. Although the oncogenic roles of maternal embryonic leucine-zipper kinase (MELK) and enhancer of zeste homologue 2 (EZH2) have been reported in accumulated research, the specific mechanistic contribution of these two ones to the stemness of GSCs remains incompletely identifiable. Here, we report that EZH2 phosphorylated by MELK binding to NF-κB methylates it in GSCs, which promotes its ability to mediate the development of glioblastoma. Clinically, the proportion of MEKL/EZH2/NF-κB axis elevates progressively during the increasing glioma grades and can be considered as the potential indicator of survival. Conversely, loss of this signaling dramatically suppresses the proliferation of GSCs. In conclusion, our findings show that the MELK/EZH2/NF-κB pathway is required for the GSCs derived neoplastic proliferation, thereby uncovering in the signaling a therapeutic candidate to treat this malignancy.