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Investigating Kinesin Kif18A as a Novel Therapeutic Target for Aggressive Cancers
Marquis, Carolyn Anne
Marquis, Carolyn Anne
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Identifying potential therapeutic targets for aggressive cancers is critical to minimizing side effects of treatments and ultimately increasing patient treatment compliance. Here we demonstrate that kinesin motor protein Kif18A has the potential to serve as a minimally toxic target for the treatment of cancers such as triple negative breast cancer (TNBC) and colorectal cancer (CRC). Kif18A inhibition reduces the proliferation of multiple TNBC cell types and one CRC cell type. While endogenous Kif18A expression does not seem to indicate cell type specific sensitivity to Kif18A inhibition, the expression levels are higher in cancer cells than in normal somatic cells. Modal chromosome number has the strongest correlation with cell sensitivity to Kif18A depletion, indicating that Kif18A is heavily involved in the regulation of mitotic progression for cells with chromosomal instability. Furthermore, cells with chromosomal instability appear to arrest in mitosis and form multipolar spindles upon Kif18A knockdown. Based on these data, Kif18A may serve as a novel therapeutic target for aggressive, chromosomally unstable cancers because of its role in regulating mitotic spindle dynamics to promote successful progression through mitosis.
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2019-01-01
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MARQUIS_Thesis.pdf
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