Fig. 8. DCA/LCA activates TGR5 signaling that regulates Ccl28 expression in the presence of β-catenin.

a HFD-fed Cdx2Apc^f/w mice were colonized with BF BSH^low or BF BSH^high for 12 weeks (n = 8 mice for BF BSH^low; n = 10 mice for BF BSH^high). Relative expression of Fxr, Tgr5 and Vdr, as well as their target genes, in colon tumor tissues. Mann–Whitney U test with two-sided. b Relative expression of Fxr, Tgr5 and Vdr in colon non-tumor (NT) and tumor (T) tissues (n = 11 independent samples for NT; n = 8 independent samples for T). Mann–Whitney U test with two-sided. c–e Cdx2Apc^f/w and Cdx2Tgr5^−/−Apc^f/w mice were fed with HFD for over 10 weeks, and then the colon tumors were used for colon organoid isolation and further culturing (n = 3 independent samples /group). c Relative expression of Tgr5. d Representative images of colon tumor-derived organoids at day 3 after passage. Scale bars: 200 μm. e Relative expression of $\mathrm{\beta }$-catenin target genes. Mann–Whitney U test with two-sided. f Isolated colon tumor organoids were treated with DMSO or MSAB (10 μM, a β-catenin protein degrader) overnight (n = 3 technical replicates/group). Relative expression of Ccl28. Two-tailed Student’s t test. g, h Cdx2Apc^f/w and Cdx2Tgr5^−/−Apc^f/w mice were fed with a HFD for over 10 weeks, and then the colon tumors were used for colon organoid isolation and further culturing (n = 3 technical replicates/group). g Relative expression of Ccl28. Two-tailed Student’s t test. h Relative expression of Ccl28 under DMSO, DCA (100 μM), LCA (100 μM), MSAB treatment overnight. Kruskal–Wallis test with Dunn’s post hoc test. i Diagram that uncovers that DCA/LCA-TGR5 signaling regulates Ccl28 expression in the presence of $\mathrm{\beta }$-catenin in colon cancer cell. Created with BioRender.com. Data are presented as mean values +/− SEM in (a–c, e–h). Source data are provided as a Source Data File for Fig. 8.