期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 7, 期 304, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aac6762
关键词
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资金
- NIH [NS073610, CA172986, NS066955, EB016071, K08CA155764, GM108743, GM112895, CA154130, CA169117, CA171652, NS087913, NS089272]
- Research Programs Committees of Cleveland Clinic
- James S. McDonnell Foundation
- American Brain Tumor Association Basic Research Fellowship
- Ohio Cancer Research Award
- Markey Cancer Center [P30CA177558]
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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