Xie, QiWu, QiulianMack, Stephen C.Yang, KailinKim, LeoHubert, Christopher G.Flavahan, William A.Chu, ChengweiBao, ShidengRich, Jeremy N.2015-09-012015Xie, Qi, Qiulian Wu, Stephen C. Mack, Kailin Yang, Leo Kim, Christopher G. Hubert, William A. Flavahan, Chengwei Chu, Shideng Bao, and Jeremy N. Rich. 2015. “CDC20 maintains tumor initiating cells.” Oncotarget 6 (15): 13241-13254.1949-2553http://nrs.harvard.edu/urn-3:HUL.InstRepos:21462670Glioblastoma is the most prevalent and lethal primary intrinsic brain tumor. Glioblastoma displays hierarchical arrangement with a population of self-renewing and tumorigenic glioma tumor initiating cells (TICs), or cancer stem cells. While non-neoplastic neural stem cells are generally quiescent, glioblastoma TICs are often proliferative with mitotic control offering a potential point of fragility. Here, we interrogate the role of cell-division cycle protein 20 (CDC20), an essential activator of anaphase-promoting complex (APC) E3 ubiquitination ligase, in the maintenance of TICs. By chromatin analysis and immunoblotting, CDC20 was preferentially expressed in TICs relative to matched non-TICs. Targeting CDC20 expression by RNA interference attenuated TIC proliferation, self-renewal and in vivo tumor growth. CDC20 disruption mediated its effects through induction of apoptosis and inhibition of cell cycle progression. CDC20 maintains TICs through degradation of p21CIP1/WAF1, a critical negative regulator of TICs. Inhibiting CDC20 stabilized p21CIP1/WAF1, resulting in repression of several genes critical to tumor growth and survival, including CDC25C, c-Myc and Survivin. Transcriptional control of CDC20 is mediated by FOXM1, a central transcription factor in TICs. These results suggest CDC20 is a critical regulator of TIC proliferation and survival, linking two key TIC nodes – FOXM1 and p21CIP1/WAF1 — elucidating a potential point for therapeutic intervention.en-UScancer stem cellglioblastomagliomatumor initiating cellCDC20Journal Article2015-09-0110.18632/oncotarget.3676