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.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Recommended Citation
Marquis, Carolyn Anne, "Investigating Kinesin Kif18A as a Novel Therapeutic Target for Aggressive Cancers" (2019). UVM Patrick Leahy Honors College Senior Theses. 286.
https://scholarworks.uvm.edu/hcoltheses/286
Comments
The full version of the thesis will be released in May of 2021.