Fig. 1.

SUMOylation inhibition suppresses the growth of KRAS-mutant cancers. A The SUMOylation cycle and inhibition by TAK-981. SUMO, small ubiquitin-like modifier; SAE, SUMO-activating enzyme; UBC9, ubiquitin conjugation enzyme 9; SENP, SUMO-specific protease. B Immunoblotting of HCT116 cells treated with various concentrations of TAK-981 for 4 h. SAE2-SUMO conjugation was assessed using a SUMOylation assay kit and SAE2 antibody. C Sensitivity of human and mouse KRAS mutant cell lines to TAK-981. Cells were treated with nine different concentrations of TAK-981, threefold dilutions from 10 µM to 1.5 nM, or without TAK-981 for 72 h (n = 6 per dose). The half-maximal inhibitory concentration (IC₅₀) was calculated using GraphPad Prism 9. The Y-axis represents the Y-axis of the TAK-981 IC₅₀ in each cell line. The blue and red bars are visually classified as ‘sensitive’ and ‘resistant’, respectively. D, E Immunocompetent or immunodeficient mouse models using CMT167 cells. The mice were treated with vehicle (control) or TAK-981 (25 mg/kg, i.p., twice a week). Tumor volumes were plotted over time from treatment initiation (n ≥ 6 per group; mean ± s.e.m.). *p < 0.05 (unpaired t-test)