| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 11, Iss 11, Pp 1809-1821 (2015) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2015.05.027 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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