Yin, Jinlong Park, Gunwoo Kim, Tae Hoon Hong, Jun Hee Kim, Youn-Jae Jin, Xiong Kang, Sangjo Jung, Ji-Eun Kim, Jeong-Yub Yun, Hyeongsun Lee, Jeong Eun Kim, Minkyung Chung, Junho Kim, Hyunggee Nakano, Ichiro Gwak, Ho-Shin Yoo, Heon Yoo, Byong Chul Kim, Jong Heon Hur, Eun-Mi Lee, Jeongwu Lee, Seung-Hoon Park, Myung-Jin Park, Jong Bae 2024-01-20T07:03:56Z 2024-01-20T07:03:56Z 2021-09-05 2015-05 1544-9173 https://pubs.kist.re.kr/handle/201004/125501 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. English PUBLIC LIBRARY SCIENCE GROWTH-FACTOR RECEPTOR GLIOBLASTOMA CELLS NOTCH NICHE IDENTIFICATION PATHWAY GENE MAINTENANCE ACTIVATION RESISTANCE Pigment Epithelium-Derived Factor (PEDF) Expression Induced by EGFRvIII Promotes Self-renewal and Tumor Progression of Glioma Stem Cells Article 10.1371/journal.pbio.1002152 1 PLOS BIOLOGY, v.13, no.5 PLOS BIOLOGY 13 5 scie scopus 000355305600011 2-s2.0-84930671246 Biochemistry & Molecular Biology Biology Biochemistry & Molecular Biology Life Sciences & Biomedicine - Other Topics Article GROWTH-FACTOR RECEPTOR GLIOBLASTOMA CELLS NOTCH NICHE IDENTIFICATION PATHWAY GENE MAINTENANCE ACTIVATION RESISTANCE EGFR