Figure 1. Lkb1 deletion drives SCC transition and tumour progression in established KRAS tumours.

(a) Schematic of the four cohorts of mice used in this study: (1) KRAS activation with Lkb1 deletion at the same time (FlpO+Tam), (2) KRAS activation followed by Lkb1 deletion after 2 weeks (FlpO-2weeks-Tam), (3) KRAS activation followed by Lkb1 deletion after 10 weeks (FlpO-10 weeks-Tam) and (4) KRAS activation alone (FlpO). (b) Kaplan–Meier survival of the four cohorts, n indicated in the figure, P<0.0001 between FlpO+Tam and 2-week Tam, P=0.0081 between 10-week Tam and FlpO. P values in b represent log-rank test. (c) Percentage of mice with at least one purely squamous lesion as determined by histology at end point in the four cohorts, n and P-values indicated in the figure, P-values represent χ²-test. (d) Haematoxylin and eosin staining of tumours at 10 weeks post FlpO show only adenocarcinoma histology. Scale bar, 50 μm. (e) Haematoxylin and eosin staining of tumours at 20 weeks post tamoxifen shows tumours that are undergoing transition from adenocarcinoma to squamous cell carcinoma histology, scale bar, 50 μm. (f) Validation of tumour subtyping by immunohistochemistry for TTF1 (NKX2.1), KRT5, p63, and SOX2. Scale bar, 50 μm. See also Supplementary Fig. 1a–c.