Cell Reports
(Jun 2015)
A CDC20-APC/SOX2 Signaling Axis Regulates Human Glioblastoma Stem-like Cells
Diane D. Mao,
Amit D. Gujar,
Tatenda Mahlokozera,
Ishita Chen,
Yanchun Pan,
Jingqin Luo,
Taylor Brost,
Elizabeth A. Thompson,
Alice Turski,
Eric C. Leuthardt,
Gavin P. Dunn,
Michael R. Chicoine,
Keith M. Rich,
Joshua L. Dowling,
Gregory J. Zipfel,
Ralph G. Dacey,
Samuel Achilefu,
David D. Tran,
Hiroko Yano,
Albert H. Kim
Affiliations
Diane D. Mao
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
Amit D. Gujar
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
Tatenda Mahlokozera
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
Ishita Chen
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
Yanchun Pan
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
Jingqin Luo
Division of Biostatistics, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Taylor Brost
Program in Molecular Cell Biology, Washington University School of Medicine, St. Louis, MO 63110, USA
Elizabeth A. Thompson
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
Alice Turski
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
Eric C. Leuthardt
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
Gavin P. Dunn
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
Michael R. Chicoine
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
Keith M. Rich
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
Joshua L. Dowling
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
Gregory J. Zipfel
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
Ralph G. Dacey
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
Samuel Achilefu
Molecular Imaging Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA
David D. Tran
Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA
Hiroko Yano
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
Albert H. Kim
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
DOI
https://doi.org/10.1016/j.celrep.2015.05.027
Journal volume & issue
Vol. 11,
no. 11
Abstract
Read online
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.
WeChat QR code
Close
