Research ArticleCancer

The mitotic kinesin KIF11 is a driver of invasion, proliferation, and self-renewal in glioblastoma

Science Translational Medicine  09 Sep 2015:
Vol. 7, Issue 304, pp. 304ra143
DOI: 10.1126/scitranslmed.aac6762

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Shutting off cancer’s motor

Glioblastoma is a common and aggressive brain tumor, which is very difficult to treat. Two of the mechanisms that contribute to its lethality are proliferation of the tumor cells and their invasion into normal brain tissue. Although these are usually thought to be independent processes, Venere et al. show that a molecular motor called KIF11 plays a role in both. By inhibiting KIF11 with a small molecule, the authors were able to block the proliferation and invasion of glioblastoma cells and to prolong survival in mouse models of this disease. These findings, together with the availability of a KIF11 inhibitor that’s safe for human use, suggest KIF11 as a viable therapeutic target for treating glioblastoma in patients.

Abstract

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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