| Literature DB >> 26074073 |
Diane D Mao1, Amit D Gujar1, Tatenda Mahlokozera2, Ishita Chen1, Yanchun Pan1, Jingqin Luo3, Taylor Brost4, Elizabeth A Thompson1, Alice Turski1, Eric C Leuthardt1, Gavin P Dunn5, Michael R Chicoine6, Keith M Rich6, Joshua L Dowling6, Gregory J Zipfel6, Ralph G Dacey6, Samuel Achilefu7, David D Tran8, Hiroko Yano9, Albert H Kim10.
Abstract
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.Entities:
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Year: 2015 PMID： 26074073 PMCID： PMC4481182 DOI： 10.1016/j.celrep.2015.05.027
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423