Role of Kinesin Molecular Motor Proteins in Cancer

Kinesin superfamily proteins, or KIFs, are microtubule-dependent molecular motors whose movement is critical to a variety of cellular processes including mitosis, meiosis, and axonal transport. So far, 45 KIF genes grouped into 15 families have been identified, and at least twice as many proteins are thought to exist due to alternative splicing1. KIFs transport cargo along microtubules much like a train moves along a rail, using the energy generated from the hydrolysis of ATP to drive conformational changes that produce motility2.

Given the critical role of KIFs in mitosis, and the fact that tumor growth is characterized by out-of-control mitosis, it is perhaps not surprising that KIFs have been linked to cancer. In fact, members of nearly all KIF families have been implicated in tumor growth, and levels of several KIFs are altered in various cancers3. For example, KIF11 is highly expressed in chronic myeloid leukemia4, and its overexpression leads to tumor growth in mice5. In addition, KIF4A is overexpressed in cervical cancer6, and has been identified as a potential prognostic biomarker for lung cancer7.

Inhibitors of two KIFs are currently being tested in cancer clinical trials – KIF10 (or CENP-E) and KIF11 (also known as EGF5) – and over 38 trials have been completed or are currently ongoing8. The KIF10 inhibitor GSK923295, which induces cell cycle arrest and subsequent cell death, has showed promise in preclinical studies, as well as in a phase I trial that examined the drug's safety and tolerability9,10. At least six KIF11-targeting drugs are currently under evaluation for the treatment multiple cancers, including prostate, breast, and renal cancer as well as leukemia8. Although KIF10 and KIF11 inhibitors have been the best studied to date, several other KIFs are also potential anticancer targets with therapeutics under development.

Detection of human KIF14 (orange) in formaldehyde-fixed HeLa cells by ICC-IF.

Antibody: Rabbit anti-KIF14 (IHC-00475). Secondary: DyLight® 550-conjugated goat anti-rabbit IgG (A120-201D3). Counterstain: Wheat Germ Agglutinin, Phalloidin Alexa Fluor® 488-conjugated (green) and DAPI (blue).

Detection of human EG5/KIF11 by WB of immunoprecipitates from 293T lysate.

Detection of human EG5/KIF11 by WB of immunoprecipitates from 293T lysate. Antibodies: Rabbit anti-EG5/KIF11 (A301-076A & A301-075A). Secondary: ReliaBLOT® reagents (WB120).


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