Fig. 2: SNAIL does not promote classical APC loss-of-function and serrated KRASG12D-driven intestinal cancer progression.
From: Non-canonical functions of SNAIL drive context-specific cancer progression
a Strategy to activate Snail expression in intestinal epithelium in the Villin-Cre;Apclox/+ (termed VApcΔInt) model of intestinal cancer. b Kaplan-Meier survival curves of Villin-Cre;Apclox/+;LSL-R26Snail/+ (termed VApcΔInt;SnailKI/+; n = 10, median survival 419 days) and VApcΔInt mice (n = 8, median survival 355 days); p = 0.12, log-rank test. c qRT-PCR of Snail mRNA expression normalized to Cyclophilin A in intestinal tumours of VApcΔInt (n = 3) and VApcΔInt;SnailKI/+ (n = 4) endpoint mice (Mean ± SEM; **p = 0.0035, unpaired two-tailed t-test with We’ch’s correction). d Number of adenomas in VApcΔInt (n = 8) and VApcΔInt;SnailKI/+ (n = 9) endpoint mice. Mean ± SEM, p = 0.08, Mann-Whitney two-tailed test. e Percentage of carcinoma-bearing mice (left) and carcinoma number (right) in VApcΔInt (n = 8) and VApcΔInt;SnailKI/+ (n = 9) endpoint mice. Left, two-tailed Fisher’s exact test, p > 0.9999; right, Mann-Whitney two-tailed test, mean ± SEM, p = 0.14. f Representative H&E and Ki67 staining of invasive intestinal carcinoma of three VApcΔInt and VApcΔInt;SnailKI/+ mice. g Strategy to express Snail in intestinal epithelium in the Villin-Cre;LSL-KrasG12D/+ model (termed VKrasG12D/+) of intestinal cancer. h Kaplan-Meier survival curves of VKrasG12D/+ (n = 5, median survival 354 days) and Villin-Cre;KrasG12D/+;LSL-R26Snail/+ (termed VKrasG12D/+;SnailKI/+) mice (n = 5, median survival 502 days); p = 0.29, log-rank test. i qRT-PCR of Snail mRNA expression in the intestine of VKrasG12D/+ (n = 5) and VKrasG12D/+;SnailKI/+ endpoint mice (n = 3). Mean ± SEM, **p = 0.005, unpaired two-tailed t-test with Welch’s correction. j Number of adenomas in VKrasG12D/+ (n = 5) and VKrasG12D/+;SnailKI/+ (n = 5) endpoint mice. Mean ± SEM, Mann-Whitney two-tailed test; p = 0.795 (ns, not significant). k Representative H&E and Ki67 staining of intestinal adenoma in three VKrasG12D/+ and VkrasG12D/+;SnailKI/+ mice. l Percentage of carcinoma-bearing mice (left) and carcinoma number (right) in VKrasG12D/+ (n = 5) and VKrasG12D/+;SnailKI/+ (n = 5) endpoint mice. Left, two-tailed Fisher’s exact test (p > 0.9999); right, two-tailed Student’s t-test (p = 0.72), mean ± SEM. m Representative H&E staining of intestinal carcinoma in two VKrasG12D/+ and three VKrasG12D/+;SnailKI/+ mice. n Pathological grading of intestinal carcinomas from VApcΔInt (n = 44), VApcΔInt;SnailKI/+ (n = 21), VKrasG12D/+ (n = 2), VKrasG12D/+;SnailKI/+ (n = 4), VBrafV637E/+ (n = 8) and VBrafV637E/+;SnailKI/+ (n = 6) mice; two-tailed Fisher’s exact test. FC, fold change; ns, not significant; scale bars, 50μm for all images. Source data are provided in the Source Data file.
