Fig. 6: Wild-type Kras deletion alters progression and metastasis of KPN tumours. | Nature Communications

Fig. 6: Wild-type Kras deletion alters progression and metastasis of KPN tumours.

From: KRAS allelic imbalance drives tumour initiation yet suppresses metastasis in colorectal cancer in vivo

Fig. 6

a Kaplan–Meier survival curve of Kras+/G12D Trp53fl/fl Rosa26N1icd/+ (KPN) and Krasfl/G12D Trp53fl/fl Rosa26N1icd/+ (KPN KF) mice aged until clinical endpoint (KPN, n = 10, 5M, 5F, KPN KF, n = 12, 6M, 6F) ***P = 2 × 10-4, log-rank (Mantel-Cox) test. b Representative H&E images of primary tumour and metastasis (liver) of mice from (a). Scale, 200 μm. c Incidence of metastasis (%) in KPN and KPN KF mice aged until clinical endpoint (KPN, n = 11, 6M, 5F; KPN KF, n = 11, 5M, 6F) ****P = 1 × 10-15, two-tailed chi-square test. d GSEA of hallmark WNT-β-Catenin signalling in KPN KF tumours compared to KPN. X-axis shows normalised enrichment score (NES), and the P value (computed and corrected for multiple testing using the Benjamini–Hochberg procedure). e Representative Notum in situ hybridisation (ISH) in KPN and KPN KF tumours. Scale, 100 μm. f Boxplots showing Notum (ISH) positive cells per tumour (%) of KPN and KPN KF tumours (KPN, n = 7, 2M, 5F; KPN KF, n = 5, 2M, 3F). **P = 0.0013. g Dotplot showing neutrophils percentage in systemic blood of KPN and KPN KF mice aged to clinical endpoint (KPN, n = 8, 6M, 2F; KPN KF, n = 7, 5M, 2F). ***P = 0.0006. h Representative Cxcl5 ISH in KPN and KPN KF tumours. Representative of five mice per genotype. Scale, 100 μm. i Boxplots showing Cxcl5 positive cells per tumour (%) of KPN and KPN KF tumours (KPN, n = 6, 2M, 4F; KPN KF, n = 5, 2M, 3F). *P = 0.0411. j Volcano plot of differentially expressed genes in organoids derived from KPN KF tumours. k Relative expression of Tgfβ ligands and chemokines from organoids derived from KPN and KPN KF tumours. Data are mean ± s.e.m. KPN, n = 3, 3M; KPN KF, n = 4, 1M, 3F. l Representative αSMA (alpha-smooth muscle actin) and Sirius Red staining of KPN and KPN KF tumours. Scale, 200 µm. m Boxplots showing Sirius Red positivity (%) and αSMA positive cells (%) of ageing or vehicle-treated KPN and KPN KF tumours (KPN n = 7, 2M, 5F; KPN KF n = 8, 4M, 4F). *P = 0.0103. f, i and m boxes depict interquartile range, central line indicates median and whiskers indicate minimum/maximum values. f, g, i and m are one-way Mann–Whitney U tests. Source data are provided as a Source Data file.

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