Downregulation of TLX induces TET3 expression and inhibits glioblastoma stem cell self-renewal and tumorigenesis

被引：68

作者：

Cui, Qi ^{[1
,2
]}

Yang, Su ^{[1
,2
]}

Ye, Peng ^{[1
]}

Tian, E. ^{[1
]}

Sun, Guoqiang ^{[1
]}

Zhou, Jiehua ^{[3
]}

Sun, Guihua ^{[4
]}

Liu, Xiaoxuan ^{[5
]}

Chen, Chao ^{[5
]}

Murai, Kiyohito ^{[1
]}

Zhao, Chunnian ^{[1
]}

Azizian, Krist T. ^{[3
]}

Yang, Lu ^{[6
]}

Warden, Charles ^{[6
]}

Wu, Xiwei ^{[6
]}

D'Apuzzo, Massimo ^{[7
]}

Brown, Christine ^{[8
]}

Badie, Behnam ^{[9
]}

Peng, Ling ^{[5
]}

Riggs, Arthur D. ^{[4
]}

Rossi, John J. ^{[2
,3
]}

Shi, Yanhong ^{[1
,2
]}

机构：

[1] City Hope Natl Med Ctr, Beckman Res Inst, Dept Dev & Stem Cell Biol, Div Stem Cell Biol Res,Canc Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA

[2] City Hope Natl Med Ctr, Beckman Res Inst, Irell & Manella Grad Sch Biol Sci, 1500 E Duarte Rd, Duarte, CA 91010 USA

[3] City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol & Cellular Biol, 1500 E Duarte Rd, Duarte, CA 91010 USA

[4] City Hope Natl Med Ctr, Beckman Res Inst, Dept Diabet & Metab Dis Res, 1500 E Duarte Rd, Duarte, CA 91010 USA

[5] Aix Marseille Univ, CNRS, UMR 7325, Ctr Interdisciplinaire Nanosci Marseille, F-13288 Marseille, France

[6] City Hope Natl Med Ctr, Beckman Res Inst, Integrat Genom Core, 1500 E Duarte Rd, Duarte, CA 91010 USA

[7] City Hope Natl Med Ctr, Beckman Res Inst, Dept Pathol, 1500 E Duarte Rd, Duarte, CA 91010 USA

[8] City Hope Natl Med Ctr, Beckman Res Inst, Dept Hematol & Hematopoiet Cell Transplantat, 1500 E Duarte Rd, Duarte, CA 91010 USA

[9] City Hope Natl Med Ctr, Beckman Res Inst, Dept Surg, 1500 E Duarte Rd, Duarte, CA 91010 USA

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

美国国家卫生研究院;

关键词：

NUCLEAR RECEPTOR TLX; CANCER; 5-HYDROXYMETHYLCYTOSINE; DENDRIMERS; DELIVERY; NANOPARTICLES; ABNORMALITIES; NEUROGENESIS; HYPOTHESIS; CONVERSION;

D O I：

10.1038/ncomms10637

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Glioblastomas have been proposed to be maintained by highly tumorigenic glioblastoma stem cells (GSCs) that are resistant to current therapy. Therefore, targeting GSCs is critical for developing effective therapies for glioblastoma. In this study, we identify the regulatory cascade of the nuclear receptor TLX and the DNA hydroxylase Ten eleven translocation 3 (TET3) as a target for human GSCs. We show that knockdown of TLX expression inhibits human GSC tumorigenicity in mice. Treatment of human GSC-grafted mice with viral vector-delivered TLX shRNA or nanovector-delivered TLX siRNA inhibits tumour development and prolongs survival. Moreover, we identify TET3 as a potent tumour suppressor downstream of TLX to regulate the growth and self-renewal in GSCs. This study identifies the TLX-TET3 axis as a potential therapeutic target for glioblastoma.

引用

页数：15

共 58 条

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