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Pigment Epithelium-Derived Factor (PEDF) Expression Induced by EGFRvIII Promotes Self-renewal and Tumor Progression of Glioma Stem Cells
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نویسنده
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yin j. ,park g. ,kim t.h. ,hong j.h. ,kim y.-j. ,jin x. ,kang s. ,jung j.-e. ,kim j.-y. ,yun h. ,lee j.e. ,kim m. ,chung j. ,kim h. ,nakano i. ,gwak h.-s. ,yoo h. ,yoo b.c. ,kim j.h. ,hur e.-m. ,lee j. ,lee s.-h. ,park m.-j. ,park j.b.
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منبع
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plos biology - 2015 - دوره : 13 - شماره : 5
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چکیده
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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. © 2015 yin et al.
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آدرس
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department of system cancer science,graduate school of cancer science and policy,national cancer center,goyang,south korea,specific organs cancer branch,research institute and hospital,national cancer center,goyang, South Korea, department of system cancer science,graduate school of cancer science and policy,national cancer center,goyang,south korea,specific organs cancer branch,research institute and hospital,national cancer center,goyang, South Korea, specific organs cancer branch,research institute and hospital,national cancer center,goyang, South Korea, specific organs cancer branch,research institute and hospital,national cancer center,goyang, South Korea, specific organs cancer branch,research institute and hospital,national cancer center,goyang, South Korea, department of biotechnology,school of life sciences and biotechnology university,seoul, South Korea, specific organs cancer branch,research institute and hospital,national cancer center,goyang, South Korea, specific organs cancer branch,research institute and hospital,national cancer center,goyang,south korea,department of biotechnology,school of life sciences and biotechnology university,seoul, South Korea, divisions of radiation cancer research,research center for radio-senescence institute of radiological and medical sciences,seoul,south korea,department of pathology,college of medicine university,seoul, South Korea, department of system cancer science,graduate school of cancer science and policy,national cancer center,goyang,south korea,specific organs cancer branch,research institute and hospital,national cancer center,goyang, South Korea, department of system cancer science,graduate school of cancer science and policy,national cancer center,goyang,south korea,cancer cell and molecular biology branch,research institute and hospital,national cancer center,goyang, South Korea, department of system cancer science,graduate school of cancer science and policy,national cancer center,goyang, South Korea, department of biochemistry and molecular biology,seoul national university,college of medicine,seoul,south korea,department of cancer biology,seoul national university college of medicine,seoul, South Korea, department of biotechnology,school of life sciences and biotechnology university,seoul, South Korea, department of neurological surgery,the ohio state university,columbus,oh,united states,james comprehensive cancer center,the ohio state university,columbus,oh, United States, specific organs cancer branch,research institute and hospital,national cancer center,goyang, South Korea, department of system cancer science,graduate school of cancer science and policy,national cancer center,goyang,south korea,specific organs cancer branch,research institute and hospital,national cancer center,goyang, South Korea, colorectal cancer branch,research institute and hospital,national cancer center,goyangi, South Korea, department of system cancer science,graduate school of cancer science and policy,national cancer center,goyang,south korea,cancer cell and molecular biology branch,research institute and hospital,national cancer center,goyang, South Korea, center for neuroscience,brain science institute institute of science and technology,seoul,south korea,department of neuroscience university of science and technology,daejeon, South Korea, department of stem cell biology and regenerative medicine,lerner research institute,cleveland clinic,cleveland,oh, United States, department of system cancer science,graduate school of cancer science and policy,national cancer center,goyang,south korea,specific organs cancer branch,research institute and hospital,national cancer center,goyang, South Korea, divisions of radiation cancer research,research center for radio-senescence institute of radiological and medical sciences,seoul, South Korea, department of system cancer science,graduate school of cancer science and policy,national cancer center,goyang,south korea,specific organs cancer branch,research institute and hospital,national cancer center,goyang, South Korea
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Authors
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