Fig. 2: Early BM lesions reactivate the zone 2-specific IGFBP2–mTOR–CCND1 axis.
From: Hepatic zonation determines tumorigenic potential of mutant β-catenin
a, Schematic to treat BM lesions with rapamycin. b, Quantification of β-catenin+ lesions PFV. The bars are mean ± s.d. One-tailed Mann–Whitney test was used to determine significance. For biological replicates, n = 6 mice per treatment. c, Representative image of β-catenin IHC (n = 6). d, Schematic to treat BM lesions with rapamycin for a transient 30-day period. e, Liver-to-body weight ratio (LW:BW), tumour scoring, tumour-free survival and liver macroscopic images of BM livers treated with rapamycin or vehicle. A log-rank (Mantel–Cox) test and one-tailed Student’s t-tests were used to determine significance. The bars are mean ± s.d. For biological replicates, n = 9 for vehicle and n = 9 for rapamycin. f, Schematic to treat BM lesions with AAV8.U6.Igfbp2-shRNA or AAV8.U6.scramble-shRNA. g, Quantification of β-catenin+ lesions PFV. The bars are mean ± s.d. A one-tailed Student’s t-test was used to determine significance. For biological replicates, n = 8 mice per treatment. h, Representative image of β-catenin IHC (n = 8). i, Schematic and time course of experiment recombining Ctnnb1ex3-mutant, MYC-mutant and Yapfl/flTazfl/fl-mutant alleles. The illustrations of the mouse and adenovirus in panels a,d,f,i were adapted from Medical Art Servier (https://servier.com) under a CC BY 4.0 licence. j, Quantification of β-catenin+ lesions PFV. The bars are mean ± s.d. A one-tailed Mann–Whitney test was used to determine significance. For biological replicates, n = 5 for Yap+/+Taz+/+ and n = 10 for Yapfl/flTazfl/fl. k, Representative image of β-catenin IHC (n = 5). The dashed lines mark β-catenin+ lesions (c,h,k). Scale bars, 100 μm (c,h,k), 1 cm (e).
