Figure 4. PARP1 suppression promotes metastasis of aneuploid cancer cells.

(A) PARP1 levels in indicated cell lines. (B-C) SCNA-normalized PARP1 RNA or protein levels in pan-cancer (B) or in colon cancer cell lines (C) with different aneuploidy degrees. (D) PARP1 protein in HT29 cells ± PARP1 overexpression. (E) Relative viability of HT29-mCherry-EV to HT29-GFP-PARP1 when co-cultured ± H₂O₂ (2 mM, 24h). (F) PARP1 protein in HCT116 and DLD1 cells ± PARP1 knockdown. (G) Relative viability of control vs PARP1-knockdown cells when co-cultured ± H₂O₂ (2 mM, 24h). (H-I) Bioluminescence images (BLI) of NSG mice with DLD1 or HCT116 ± PARP1 knockdown. Left: representative images. Middle: total flux over time. Right: maximum values. Mean ± SD, n=5 mice/group. Crosses indicate endpoints. (J) BLI of immune-intact mice with aneuploid mouse KP lung cancer cells ± PARP1 overexpression. Left: representative images. Right: maximum total flux signal. Mean + SD, n=5 mice/group. (K) PARP1 RNA levels in TCGA COREAD patients without PARP1 SCNA. (L) Kaplan-Meier survival of TCGA COREAD patients stratified by PARP1 expression. (M) PARP1 RNA levels in primary COREAD tumors and their paired metastases (n=15 patients, GSE131418). (N) PARP1 RNA in unpaired primary tumors versus metastases of COREAD patients (discovery cohort: 333 primary, 184 metastases; validation cohort: 545 primary, 72 metastases, GSE131418). One-way ANOVA with Tukey’s test (A, B, K). Kruskal-Wallis test, followed by one-tailed t-test comparing low vs high aneuploidy groups (C). Unpaired t-test (E, G, N). Two-tailed Mann-Whitney test (H-I). One-tailed Mann-Whitney test (J). Log-rank (Mantel-Cox) test (L). One Sample Wilcoxon signed-rank test (M).