| Literature DB >> 19896441 |
Hiroaki Ikushima1, Tomoki Todo, Yasushi Ino, Masamichi Takahashi, Keiji Miyazawa, Kohei Miyazono.
Abstract
Despite 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-beta signaling plays an essential role in retention of stemness of glioma-initiating cells (GICs) and describe the underlying mechanism for it. TGF-beta induced [corrected] expression of Sox2, a stemness gene, and this induction was mediated by Sox4, a direct TGF-beta target gene. Inhibitors of TGF-beta 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-beta signaling inhibitor exhibited less lethal potency in intracranial transplantation assay. These results identify an essential pathway for GICs, the TGF-beta-Sox4-Sox2 pathway, whose disruption would be a therapeutic strategy against gliomas.Entities:
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Year: 2009 PMID： 19896441 DOI： 10.1016/j.stem.2009.08.018
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633