驱动蛋白
细胞生物学
微管
核分裂突变
胶质母细胞瘤
细胞周期
细胞
作者
Monica Venere,Craig Horbinski,James F. Crish,Xun Jin,Amit Vasanji,Jennifer Major,Amy C. Burrows,Cathleen Chang,John Prokop,Q Wu,Peter A. Sims,Peter Canoll,Matthew K. Summers,Steven S. Rosenfeld,Jeremy N. Rich
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2015-09-09
卷期号:7 (304)
被引量:83
标识
DOI:10.1126/scitranslmed.aac6762
摘要
The proliferative and invasive nature of malignant cancers drives lethality. In glioblastoma, these two processes are presumed mutually exclusive and hence termed go or grow. We identified a molecular target that shuttles between these disparate cellular processes-the molecular motor KIF11. Inhibition of KIF11 with a highly specific small-molecule inhibitor stopped the growth of the more treatment-resistant glioblastoma tumor-initiating cells (TICs, or cancer stem cells) as well as non-TICs and impeded tumor initiation and self-renewal of the TIC population. Targeting KIF11 also hit the other arm of the go or grow cell fate decision by reducing glioma cell invasion. Administration of a KIF11 inhibitor to mice bearing orthotopic glioblastoma prolonged their survival. In its role as a shared molecular regulator of cell growth and motility across intratumoral heterogeneity, KIF11 is a compelling therapeutic target for glioblastoma.
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