Fig. 7: ZEB2-induced EMT and stromal factors regulate expression of a number of genes associated with stemness, invasion and anti-apoptotic response in fbxw7^ΔG organoids.

a Heat map showing an average of 84 genes expressed from triplicate pooled samples (n = 25) from fbxw7^fl/fl and fbxw7^ΔG organoids (Ep^ΔG vs. Ep^fl/fl) on day 1 (Table S2). Expression was determined by qRT-PCR and was first normalised to GAPDH followed by normalisation to fbxw7^fl/fl organoids. Downregulated genes (green), and upregulated genes (red). b qRT-PCR analysis confirming relative expression levels of a number of stem and EMT-associated genes expression in Ep^ΔG vs. Ep^fl/fl organoids. Data are mean ± SEM (*P ≤ 0.05; **P < 0.01; ***P < 0.001). Experiments were performed in triplicate for each genotype and repeated at least on three independent occasions. c Relative qRT-PCR transcript levels of the above-84-indicated genes from pooled samples (n = 15) for released Ep^ΔGorganoids from cocultured Ep^ΔGIMF^fl/fl and Ep^ΔGIMF^ΔG on day 3, as compiled into a heat map. Expression was normalised to GAPDH followed by normalisation to released Ep^ΔGorganoids from cocultured Ep^ΔGIMF^fl/fl. Downregulated genes (green), and upregulated genes (red). d qRT-PCR confirming relative expression levels of a number of stem and EMT-associated genes, in Ep^ΔGIMF^ΔG vs. Ep^ΔGIMF^fl/fl cocultured organoids. Data are mean ± SEM (**P < 0.01; ***P < 0.001). Experiments were performed in triplicate for each genotype and repeated at least on three independent occasions. e qRT-PCR analysis of Ep^ΔG vs. Ep^ΔG:Ep^Zeb2-KD organoids for genes deferentially expressed in Ep^ΔG vs. Ep^fl/fl organoids. Data are mean ± SEM (*P ≤ 0.05; **P < 0.01; ***P < 0.001). Experiments were performed in triplicate for each genotype (n = 25) and repeated at least on two independent occasions. f Intestinal/colon cancer progression/metastasis could be an effect of the loss of a controlled feedback via the FBXW7/ZEB2 complex modifying EMT and epithelial–stromal interactions