Our findings improve our understanding of the molecular mechanism underlying the maintenance of the stemness and tumorigenicity of GSCs and suggest that SMURF2Thr249 phosphorylation status could represent a novel target for drug development to treat not only gliomas but also malignant tumors associated with the aberrant expression or function of TGF-β signaling in humans. This evidence concerns the gene TGFB1 and central nervous system cancer.