Article ID Journal Published Year Pages File Type
2077986 Cell Stem Cell 2009 11 Pages PDF
Abstract

SummaryDespite aggressive surgery, radiotherapy, and chemotherapy, treatment of malignant glioma remains formidable. Although the concept of cancer stem cells reveals a new framework of cancer therapeutic strategies against malignant glioma, it remains unclear how glioma stem cells could be eradicated. Here, we demonstrate that autocrine TGF-β signaling plays an essential role in retention of stemness of glioma-initiating cells (GICs) and describe the underlying mechanism for it. TGF-β induced expression of Sox2, a stemness gene, and this induction was mediated by Sox4, a direct TGF-β target gene. Inhibitors of TGF-β signaling drastically deprived tumorigenicity of GICs by promoting their differentiation, and these effects were attenuated in GICs transduced with Sox2 or Sox4. Furthermore, GICs pretreated with TGF-β signaling inhibitor exhibited less lethal potency in intracranial transplantation assay. These results identify an essential pathway for GICs, the TGF-β-Sox4-Sox2 pathway, whose disruption would be a therapeutic strategy against gliomas.

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