Figure 6 from Spindle Assembly Checkpoint Competency Determines Sensitivity to KIF18A Inhibition in Small Cell Lung Cancer
Year: 2026
Type: other
Abstract: SAC integrity determines cellular responses to KIF18A inhibition in SCLC. A, Schematic timeline illustrating the experimental workflow for time-lapse imaging. KIF18Ai, KIF18A inhibitor; MPS1i, MPS1 inhibitor. B, Representative time-lapse images of H2B-GFP–expressing DMS 53 cells treated with DMSO, AM-9022 (0.04 μmol/L), or AM-9022 following pretreatment with the SAC inhibitor reversine. Representative frames from the time-lapse sequences. Yellow arrows indicate mitotic cells. Scale bars, 10 μm. C, Quantification of mitotic timing in DMS 53 cells following the indicated treatments. Mitotic timing was calculated by counting frames, each frame equivalent to 4 minutes, from nuclear envelope breakdown to anaphase onset or cell death in time-lapse images. Bars represent the median, and dots indicate individual biological replicates (n = 3). P values were calculated using the Friedman test with the Dunn multiple-comparison test. ns, not statistically significant. D, Quantification of cell fate outcomes in DMS 53 cells following the indicated treatments. Bar graphs show the percentage of cells undergoing normal or abnormal mitotic exit, tripolar, or apoptosis. Dots represent individual biological replicates (n = 3). E, Proposed model depicting how SAC integrity shapes cellular responses to KIF18A inhibition in SCLC. In AM-9022–sensitive cells, KIF18A inhibition causes chromosome misalignment, prolonged SAC activation, mitotic arrest, and cell death. In contrast, resistant cells exhibit attenuated SAC signaling and are able to progress through mitosis despite KIF18A inhibition, allowing continued survival and proliferation. KD, knockdown.
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W7212078876