Fig. 5: SNAIL bypasses senescence to drive pancreatic carcinogenesis.
From: Non-canonical functions of SNAIL drive context-specific cancer progression
a Representative images of senescence-associated β-galactosidase (SA-β-gal) staining of pancreata with PanIN lesions of PKrasG12D/+ (n = 13) and PKrasG12D/+;SnailKI/+ (n = 12) mice. Scale bars, 50 μm. LG, low grade; HG, high grade. b Quantification of SA-β-gal-stained PanIN lesions from PKrasG12D/+ (n = 13) and PKrasG12D/+;SnailKI/+ (n = 12) mice. Mean ± SEM, *p < 0.0001, Mann-Whitney two-tailed test. LG, low grade; HG, high grade. c Gene set enrichment analysis (GSEA) of mRNA expression profiling of 1-month-old mice (n = 2 per genotype) computed and corrected for multiple testing using the Benjamini–Hochberg procedure (for statistical details, please see methods section) shows significant enrichment of Rb1 targets senescent genes (CHICAS_RB1_TARGETS_SENESCENT) in PKrasG12D/+;SnailKI/+ (red) vs. PKrasG12D/+ (blue) pancreata. Normalized Enrichment Score: 2.68; Nominal p-value < 0.001; False Discovery Rate (FDR) q-value < 0.001. d Representative images of SA-β-gal staining of pancreata with PanIN lesions of PKrasG12D/+;SnailKO/KO mice (n = 2). Scale bars, 50 μm. LG Low grade, HG High grade. e Viability of Human Pancreatic Duct Epithelial (HPDE) cells after activation of KRASG12D alone or in combination with SNAIL. HPDE cells transduced with lentiviral constructs for doxycycline-inducible expression of EGFP, KRASG12D ( + mock vector) or KRASG12D + SNAIL were treated with 100 ng ml-1 doxycycline. Viability was assessed by CellTiter-Glo assay after 72 h and is displayed as % of the respective untreated controls. Mean ± SEM. n = 3 independent experiments; *p = 0.033, unpaired two-tailed t-test with Welch’s correction. f Representative images of SA-β-Gal staining of HPDE cells treated for 3 days with doxycycline (100 ng ml-1) to induce activation of EGFP, KRASG12D + mock or KRASG12D + SNAIL. n = 3 independent experiments. The percentage of SA-β-gal+ cells is indicated in the upper right corner. Scale bar, 10 µm. Source data of Fig. 5 are provided in the Source Data file.
