Fig. 4

Response to JAK/STAT and MEK inhibitors in CRC molecular subtypes. a Heat map showing mutation/expression of JAK/STAT genes in relation to mutation load, LY6G6D and CD15/FUT4 expression in CRC cancer cell lines (n = 38). b A chemo-immune-sensitizer approach targeting LY6G6D and CD15/FUT4 by JAK/STAT and MEK inhibitors. Right, Log10 IC50 values for treatment of MSI and MSS CRC cell lines with ruxolitinib (JAK/STATi) and trametinib (MEKi) extracted from the Genomics of Drug Sensitivity in Cancer project. c RKO (MSI-H) and SW620 (MSS) stained with LY6G6D (green) and CD15 (red). Bottom right, basal activation of stat1, stat3, stat5 in a panel of CRC cell lines. Down left, western blotting showing expression of P-STAT5, STAT5 P-ERK1/2, ERK1/2 and LY6G6D. Down right, quantification of P-STAT5, P-ERK1/2 and LY6G6D relative to β-actin. d Cells were treated with different concentrations of momelotinib (range, 1 nM to 1 mM for 96 h) and evaluated for proliferation by MTT staining. Right, boxplot of log10 IC50 values for treatment of five CRC cell lines (RKO,HT29, SW480, SW620, HCT116) with ruxolitinib vs momelotinib. Results are representative of three biological replicates. P-value by two-tailed Student’s. P* < 0.05, **P < 0.01