High CDC20 levels increase sensitivity of cancer cells to MPS1 inhibitors.

ABSTRACT: Spindle assembly checkpoint (SAC) inhibitors are a recently developed class of drugs, which perturb chromosome segregation during cell division, induce chromosomal instability (CIN), and eventually lead to cell death. The molecular features that determine cellular sensitivity to these drugs are not fully understood. We recently reported that aneuploid cancer cells are preferentially sensitive to SAC inhibition. Here we report that sensitivity to SAC inhibition by MPS1 inhibitors is largely driven by the expression of CDC20, a main mitotic activator of the anaphase-promoting complex (APC/C), and that the effect of CDC20 is larger than that of the APC/C itself. Mechanistically, we discovered that CDC20 depletion prolongs metaphase duration, diminishes mitotic errors, and reduces sensitivity

SUBMITTER: Zheng S 

PROVIDER: S-EPMC11850905 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature