Most cancer cell lines give very modest transcriptional regulation following treatment with the SUMO activating enzyme inhibitors TAK-981 or ML-792

Modest transcriptional changes has been previously observed in solid tumor cell lines in response to inhibition of SUMOylation by ML-792 and here confirmed with TAK-981, lacking a robust induction of IFN1 genes. Comparable modulation of gene expression in HCT116, MDA-MB-231 and Colo-205 cells by TAK-981 and ML-792. Biological triplicates of HCT116, MDA-MB-231 and Colo-205 cells treated with DMSO, 1 μM ML-792 or 1 μM TAK-981 in vitro for 16 h were analyzed by RNA-Seq. The number of differentially expressed genes (DEGs) with false discovery rate corrected p- values of <0.05 and fold-change values greater than 2 are captured. The degree of gene regulation by TAK-981 is plotted against the degree of gene regulation by ML-792 for the union of their DEGs for each cell line. Data are fitted by linear regression after outliers were removed (7 DEGs from Colo- 205, r^2 = 0.951; 2 DEGs from HCT116, r^2 = 0.836; and 2 DEGs from MDA-MB-231, r^2 = 0.971). Limited and comparable upregulation of human IFN1 mRNA signature in Colo-205, and MDA-MB-231 cells, but not in HCT116 cells, following 16h of treatment with 1uM ML-792 or 1uM TAK-981, as determined by human IFN1 ssGSEA gene signature scores. In vitro treatment of the A20, B16F10, CT26 and MC38 mouse tumor cell lines with TAK-981 did not result in induction of the IFN1 pathway. The overall degree of transcriptional modulation by TAK-981 was relatively modest in the mouse tumor cell lines, with only limited overlap observed in the transcriptional responses to TAK-981, as also observed for the human solid tumor cell lines. In vitro treatment of human cell lines with DMSO, 1 uM TAK-981 or 1 uM ML-792 for 16 h. In vitro treatment of mouse cell lines with DMSO or 1 uM TAK-981 for 16 h.