Pigment Epithelium-Derived Factor (PEDF) Expression Induced by EGFRvIII Promotes Self-renewal and Tumor Progression of Glioma Stem Cells

Title
Pigment Epithelium-Derived Factor (PEDF) Expression Induced by EGFRvIII Promotes Self-renewal and Tumor Progression of Glioma Stem Cells
Authors
Jinlong Yin박건우김태훈홍준희김연재Xiong Jin강상조정지은김정엽윤형순이정은김민경정준호김형기Ichiro Nakano곽호신유헌유병철김종헌허은미이정우이승훈박명진박종배
Keywords
EGFR
Issue Date
2015-05
Publisher
PLoS biology
Citation
VOL 13, NO 5, 1-25
Abstract
Epidermal growth factor receptor variant III (EGFRvIII) has been associated with glioma stemness, but the direct molecular mechanism linking the two is largely unknown. Here, we show that EGFRvIII induces the expression and secretion of pigment epithelium-derived factor (PEDF) via activation of signal transducer and activator of transcription 3 (STAT3), thereby promoting self-renewal and tumor progression of glioma stem cells (GSCs). Mechanistically, PEDF sustained GSC self-renewal by Notch1 cleavage, and the generated intracellular domain of Notch1 (NICD) induced the expression of Sox2 through interaction with its promoter region. Furthermore, a subpopulation with high levels of PEDF was capable of infiltration along corpus callosum. Inhibition of PEDF diminished GSC self-renewal and increased survival of orthotopic tumor-bearing mice. Together, these data indicate the novel role of PEDF as a key regulator of GSC and suggest clinical implications.
URI
http://pubs.kist.re.kr/handle/201004/50379
ISSN
15457885
Appears in Collections:
KIST Publication > Article
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