Fig. 4

KLF5 is a potential driver of chromosome 13q gain in human colorectal cancer. A Comparison of the prevalence of chromosome-arm aneuploidies in colorectal tumors against all other tumors (left) and colorectal cancer cell lines against all other cancer cell lines (right). On the right side are the aneuploidies that are more common in colorectal cancer, and on the left side are the ones that are less common in colorectal cancer. Chromosome-arm 13q (in red) is the top differential aneuploidy in colorectal cancer. B Comparison of the prevalence of 13q aneuploidy between colorectal tumors and all other tumors (left) and between colorectal cancer cell lines and all other cancer cell lines (right). ****, p < 0.0001 and ****, p < 0.0001; Chi-square test. C Genome-wide comparison of differentially essential genes between colorectal cancer cell lines (n = 85) and all other cancer cell lines (n = 1407). On the right side are the genes that are more essential in other cancer cell lines, and on the left side are those that are more essential in colorectal cancer, based on a genome-wide CRISPR/Cas9 knockout screens [39]. The x-axis presents the effect size (i.e., the differential response between colorectal cell lines and other cell lines), and the y-axis presents the significance of the difference (-log10(p-value)). KLF5 (in red) is the second most differentially essential gene in colorectal cancer cell lines. D Comparison of the sensitivity to CRISPR knockout of KLF5 between colorectal cancer cell lines (n = 59) and all other cancer cell lines (n = 1041). ****, p < 0.0001; two-tailed Mann–Whitney test. E Genome-wide comparison of differentially expressed genes between colorectal tumors (n = 434) and all other tumors (on the left, n = 11,060) and between colorectal cancer cell lines (n = 85) and all other cancer cell lines (on the right, n = 1407). On the right side are the genes that are over-expressed in colorectal cancer and on the left side are those that are over-expressed in other cell lines. KLF5 (in red) significantly over-expressed in colorectal cancer. F Comparison of KLF5 mRNA levels between colorectal tumors (n = 434) and all other tumors on the left (n = 11,060) and between colorectal cancer cell lines (n = 85) and all other cancer cell lines (on the right, n = 1407). ****, p < 0.0001; two-tailed Mann–Whitney test. G Correlation between KLF5 mRNA expression and the sensitivity to KLF5 knockdown, showing that higher KLF5 expression is associated with increased sensitivity to its RNAi-mediated knockdown. ρ = − 0.39, p = 0.01; Spearman correlation. H Comparison of KLF5 mRNA levels between DLD1-WT (without trisomy of chromosome 13) and DLD1-Ts13 (with trisomy of chromosome 13) colorectal cancer cells. **, p = 0.0025; one-sample t-test. I Representative images of DLD1-WT and DLD1-Ts13 cells treated with siRNA against KLF5. DLD1-Ts13 cells proliferated more slowly, as previously reported, but were more sensitive to the knockdown after accounting for their basal proliferation rate. Cell masking (shown in yellow) was performed using live cell imaging (IncuCyte) following 72 h of treatment. Scale bar 400µm. J Quantification of the relative response to KLF5 knockdown between DLD1-WT and DLD1-Ts13, as evaluated by quantifying cell viability in cells treated with siRNA against KLF5 versus a control siRNA for 72 h. n = 3 independent experiments. *, p = 0.0346; one-sided paired t-test