Wednesday February 7th, 2024
12:30pm – 1:30pm
School of Medicine, Room 032A
Jason Stumpff, Ph.D.
Department of Molecular Physiology and Biophysics
University of Vermont
Investigating CIN as a Targetable Vulnerability in Tumor Cells
Chromosomal instability (CIN) is a hallmark of tumor cells that contributes to aggressive characteristics such as increased proliferation, metastasis, and drug-resistance. CIN is also associated with changes in the dynamics of microtubules that compromise the mitotic spindle, potentially making them more vulnerable to treatments that target mitotic spindle regulation than normal cells. In agreement with this idea, we found that a kinesin-8, KIF18A, is required for proliferation of CIN cells derived from triple negative breast cancer or colorectal cancer tumors but is not required in near-diploid cells. Following KIF18A inhibition, CIN tumor cells exhibit mitotic delays and mitotic spindle defects. However, the responses of CIN cells to KIF18A loss of function are graded and not all CIN cells are dependent on KIF18A for proliferation. Current efforts are focused on determining the mechanisms underlying sensitivity and resistance to KIF18A inhibition in CIN cells.