American Association for Cancer Research
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Supplementary Table 1 and Supplementary Figures 1 through 8 from Western Diet Deregulates Bile Acid Homeostasis, Cell Proliferation, and Tumorigenesis in Colon

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posted on 2023-03-31, 00:29 authored by Denis Dermadi, Satu Valo, Saara Ollila, Rabah Soliymani, Nina Sipari, Marjaana Pussila, Laura Sarantaus, Jere Linden, Marc Baumann, Minna Nyström

Table S1. Composition of the diets. Figure S1. Related to Western diet increases weight and induces neoplastic changes in colon paragraph in the main text. Figure S2. Venn diagrams of proteins detected and identified with two different proteomics platforms: 2D-DIGE and LS-MS. Figure S3. Related to Figure 2. Extended histological analysis of colon crypts. Figure S4. Related to Figure 3. Changes in bile acid transport pathway. Figure S5. Related to Figure 4. Volcano plot of metabolomics analysis of bile acids. Figure S6. Heatmap of comparison between fold changes in protein abundance detected in our study with 2D DIGE and RNAseq data (GSE67342). Figure S7. Network analysis of LC-MS proteomics data at 12 months, combined with metabolomics data showing expression of proteins and concentration of intracellular bile acids in WD mice, supports inactivation of SREBF2 and HNF4A, both involved in regulation of Asbt transcription. Figure S8. Abundance of MUC2 measured with LC-MS revealed increase of MUC2 in 12m WD group and reduction in 18m WD when compared to control groups.

Funding

European Research Council

Jane and Aatos Erkko Foundation

Sigrid Juselius Foundation

Finnish Cancer Organizations

Integrative Life Sciences (ILS)

History

ARTICLE ABSTRACT

Western-style diets (WD) high in fat and scarce in fiber and vitamin D increase risks of colorectal cancer. Here, we performed a long-term diet study in mice to follow tumorigenesis and characterize structural and metabolic changes in colon mucosa associated with WD and predisposition to colorectal cancer. WD increased colon tumor numbers, and mucosa proteomic analysis indicated severe deregulation of intracellular bile acid (BA) homeostasis and activation of cell proliferation. WD also increased crypt depth and colon cell proliferation. Despite increased luminal BA, colonocytes from WD-fed mice exhibited decreased expression of the BA transporters FABP6, OSTβ, and ASBT and decreased concentrations of secondary BA deoxycholic acid and lithocholic acid, indicating reduced activity of the nuclear BA receptor FXR. Overall, our results suggest that WD increases cancer risk by FXR inactivation, leading to BA deregulation and increased colon cell proliferation. Cancer Res; 77(12); 3352–63. ©2017 AACR.