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

Monica Venere, Craig Horbinski, James F. Crish, Xun Jin, Amit Vasanji, Jennifer Major, Amy C. Burrows, Cathleen Chang, John Prokop, Quilian Wu, Peter A. Sims, Peter Canoll, Matthew K. Summers, Steven S. Rosenfeld*, Jeremy N. Rich

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

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 amolecular target that shuttles between these disparate cellular processes'themolecular 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 armof 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.

Original languageEnglish (US)
Article number304ra143
JournalScience translational medicine
Volume7
Issue number304
DOIs
StatePublished - Sep 9 2015

ASJC Scopus subject areas

  • Medicine(all)

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