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

作者：Mao Diane D; Gujar Amit D; Mahlokozera Tatenda; Chen Ishita; Pan Yanchun; Luo Jingqin; Brost Taylor; Thompson Elizabeth A; Turski Alice; Leuthardt Eric C; Dunn Gavin P; Chicoine Michael R; Rich Keith M; Dowling Joshua L; Zipfel Gregory J; Dacey Ralph G; Achilefu Samuel; Tran David D; Yano Hiroko; Kim Albert H^*

来源：Cell Reports, 2015, 11(11): 1809-1821.

DOI：10.1016/j.celrep.2015.05.027

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.

• 出版日期2015-6-23