Date of Completion

2019

Document Type

Honors College Thesis

Department

Molecular Physiology and Biophysics

Thesis Type

Honors College, College of Arts and Science Honors

First Advisor

Jason Stumpff, Ph.D.

Second Advisor

Heidi Malaby, Ph.D.

Keywords

cancer, kinesin, cell division, breast cancer, mitosis, colorectal cancer

Abstract

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.

Comments

The full version of the thesis will be released in May of 2021.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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