A CDC20-APC/SOX2 Signaling Axis Regulates Human Glioblastoma Stem-like Cells

被引：87

作者：

Mao, Diane D. ^{[1
]}

Gujar, Amit D. ^{[1
]}

Mahlokozera, Tatenda ^{[1
,2
]}

Chen, Ishita ^{[1
]}

Pan, Yanchun ^{[1
]}

Luo, Jingqin ^{[3
]}

Brost, Taylor ^{[4
]}

Thompson, Elizabeth A. ^{[1
]}

Turski, Alice ^{[1
]}

Leuthardt, Eric C. ^{[1
]}

Dunn, Gavin P. ^{[1
,5
,6
,7
,8
]}

Chicoine, Michael R. ^{[1
,5
]}

Rich, Keith M. ^{[1
,5
]}

Dowling, Joshua L. ^{[1
,5
]}

Zipfel, Gregory J. ^{[1
,5
]}

Dacey, Ralph G. ^{[1
,5
]}

Achilefu, Samuel ^{[9
]}

Tran, David D. ^{[5
,10
]}

Yano, Hiroko ^{[1
,5
,11
,12
]}

Kim, Albert H. ^{[1
,5
,11
,13
]}

机构：

[1] Washington Univ, Sch Med, Dept Neurol Surg, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Program Neurosci, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Med, Div Biostat, St Louis, MO 63110 USA

[4] Washington Univ, Sch Med, Program Mol Cell Biol, St Louis, MO 63110 USA

[5] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA

[6] Washington Univ, Sch Med, Ctr Human Immunol, St Louis, MO 63110 USA

[7] Washington Univ, Sch Med, Immunotherapy Programs, St Louis, MO 63110 USA

[8] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA

[9] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Mol Imaging Ctr, St Louis, MO 63110 USA

[10] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA

[11] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

[12] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

[13] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA

来源：

CELL REPORTS | 2015年 / 11卷 / 11期

关键词：

INTEGRATED GENOMIC ANALYSIS; TUMOR-INITIATING CELLS; CYCLE PROGRESSION; SOX2; DIFFERENTIATION; INVASION; PATHWAY; GLIOMAS; IDH1; PHOSPHORYLATION;

D O I：

10.1016/j.celrep.2015.05.027

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Glioblastoma harbors a dynamic subpopulation of glioblastoma stem-like cells (GSCs) that can propagate tumors in vivo and is resistant to standard chemoradiation. Identification of the cell-intrinsic mechanisms governing this clinically important cell state may lead to the discovery of therapeutic strategies for this challenging malignancy. Here, we demonstrate that the mitotic E3 ubiquitin ligase CDC20-anaphase-promoting complex (CDC20-APC) drives invasiveness and self-renewal in patient tumor-derived GSCs. Moreover, CDC20 knockdown inhibited and CDC20 overexpression increased the ability of human GSCs to generate brain tumors in an orthotopic xenograft model in vivo. CDC20-APC control of GSC invasion and self-renewal operates through pluripotency-related transcription factor SOX2. Our results identify a CDC20-APC/SOX2 signaling axis that controls key biological properties of GSCs, with implications for CDC20-APC-targeted strategies in the treatment of glioblastoma.

引用

页码：1809 / 1821

页数：13

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