SPOPL induces tumorigenicity and stemness in glioma stem cells by activating Notch signaling

Abstract

Abstract Glioma stem cells (GSCs) have been associated with high heterogeneity, recurrence rate, and resistance to radiotherapy and chemotherapy of glioblastoma multiforme (GBM). As members of the Meprin-associated Traf homology (MATH) - Broad-complex, Tramtrack, and Bric-a-brac (BTB) protein family, both SPOPL and SPOP have been associated with cancer stem cells in various tumors. Although it has been established that SPOPL has a broader expression profile than SPOP in the human brain, whether it plays an important role in GSCs remains unclear. In the present study, analysis of SPOPL expression in GSCs, glioma cell lines, and GBM clinical specimens showed that high SPOPL expression correlated with poor prognosis. Analysis of the biological function of SPOPL in GSCs showed that SPOPL promotes the proliferation, tumorigenic and self-renewal ability of GSCs and inhibits the differentiation potential of GSCs. RNA-seq revealed that SPOPL could affect the biological functions of GSCs through activation of the Notch signaling pathway. Overall, SPOPL represents a possible molecular target for GBM treatment.