Extended Data Fig. 4: Mesenchymal-like cancers depend on CDS2 for PI synthesis.
a, CDH1 and VIM expression in ΔCDS2 lethal, ΔCDS2 nonlethal, CDS1-low (bottom quartile) and CDS1-high (top quartile) cancer cell lines (DepMap). Mann-Whitney U test was used. n = 913 cancer cell lines (657 nonlethal, 256 lethal, 345 CDS1 low, 352 CDS1 high). b, The percentage of CDS1-high cancer cell lines (DepMap) was plotted against the percentage of VIM-high or CDH1-high cancer cell lines by type. A linear regression and Pearson correlation test were added. n = 906 cancer cell lines. c, CDS1 promoter methylation in all cancer cell lines and the blood subtype (DepMap). Histograms show the distribution of CDS1 promoter methylation (top). Mann-Whitney U test was used. n = 792 cancer cell lines (72 blood). d, The gene set enrichment analysis (GSEA) results for Hallmark epithelial to mesenchymal transition. Results are from a GSEA on genome-wide CDS1 coexpression (Pearson’s r) using DepMap and TCGA data. The Benjamini-Hochberg corrected GSEA P values were used. n = 913 cancer cell lines, 11,069 patient samples. e, For 16 cancer types the calibration gene-normalized RNA expression in healthy tissue samples (GTEx) and cancer cell lines (DepMap) was compared. The cut-off for low expression of CDS1 or CDH1 expression was the bottom-tertile boundary for expression in healthy tissue samples of the same type (right). CDH1 and VIM expression were plotted as a percentage of the highest expressing cancer type included (left). Kruskal-Wallis test followed by Dunn’s test was used by type. The Pearson correlation test was used across types. n (healthy/cancer) = 2,642/70 (brain), 929/48 (blood), 653/8 (thyroid), 89/25 (kidney), 1,809/63 (skin), 226/22 (liver), 180/53 (ovarian), 578/122 (lung), 142/32 (uterus), 19/13 (cervix), 359/29 (stomach), 328/42 (pancreatic), 459/40 (breast), 1,445/28 (esophagus), 966/50 (colorectal), 245/5 (prostate). f, Left: the method for quantifying the dead cell fraction using the DNA-intercalating dye DRAQ7. Right: rescue of ΔCDS2 cell death upon overnight supplementation with 2 mM phosphatidylinositol (PI) started 11 d after transduction of BLM cells. One-way ANOVA followed by Šidák’s test was used. n = 3 replicates for 1 cancer cell line. In a-f: *P<0.05, **P<0.01, ***P<0.001.
