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

•CDC20-APC drives the invasiveness and self-renewal of glioblastoma stem-like cells•CDC20 is essential for the in vivo tumorigenicity of glioblastoma stem-like cells•CDC20-APC operates through SOX2 to control glioblastoma stem-like cell function•CDC20 is prognostic of overall survival in Proneural subtype glioblastoma patients

SummaryGlioblastoma 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.

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