Fig. 6: IL-17-induced copper uptake contributes to chemoresistance in human colon cancer.

a Immunostaining for STEAP4 expression in human normal colon and tumor colon tissue. Representative staining is shown. Scale bar, 200 µm. n = 117 biologically independent tissues from different patients. ***P = 0.0007 by two-tailed Student’s t test. b, c STEAP4, IL-17 and cleaved Caspase 3 (cCasp3) were stained on consecutive sections of the same case. Staining intensity of IL-17 and cCasp3 was plotted as a function of STEAP4 intensity. Linear regression was performed to derive the trend line, r and P value. Dotted curve indicates 90% confidence interval. Scale bar, 200 µm. n = 117 biologically independent tissues from different patients. d Analysis of XIAP shift on tissue lysates from paired normal (N), tumor (T) and metastatic tissue (M) of the same colon cancer cases. e IL-17-induced copper uptake measured by fluorescence probe in colon cancer organoids. n = 5 biologically independent cells. **P = 0.0015 by unpaired two-tailed t test. Scale bar, 100 µm. f, g Copper and XIAP are required for sustaining IL-17-induced NF-κB activation (f) and suppression of 5-FU-induced caspase-3 cleavage (g). h In-gel SOD1 activity assay on human colon cancer organoids. All data were presented as mean ± SEM. Experiments in (a−c) were performed once over 117 cases (tissue microarray). Other data represent three independent experiments with similar results.