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University of California-San Diego: Dataset Details, ID=SRP111558

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Superfund Research Program

Detection and Models of Toxicant Exposure

Center Director: Robert H. Tukey
Grant Number: P42ES010337
Funding Period: 2000-2023
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Title: FXR Regulates Intestinal Cancer Stem Cell Proliferation.

Accession Number: SRP111558

Link to Dataset: https://trace.ncbi.nlm.nih.gov/Traces/sra/?study=SRP111558

Repository: Sequence Read Archive (SRA)

Data Type(s): Nucleotide Sequence

Experiment Type(s): Transcriptome analysis

Organism(s): Mus musculus

Summary: We report increased levels of the hydrophobic bile acid T- MCA during intestinal cancer progression using the APCmin/+ mouse tumor model. Likewise, HFD induced a shift in BA composition towards T- MCA. T- MCA is an antagonist of the Farnesoid X Receptor (FXR), which is reflected in downregulation of the FXR transcriptional network during cancer progression. We found that the modified gut-biased FXR agonist Fexaramine D (FexD) protects against tumor progression. FexD lowers T- MCA levels and restores FXR activity. We find that proliferation of intestinal organoids was stimulated by T- MCA but inhibited by FexD. In summary, we demonstrate that preservation of FXR signaling and maintenance of a healthy BA pool are paramount in the prevention/treatment of colon cancer.

Publication(s) associated with this dataset:
  • Fu T, Coulter S, Yoshihara E, Oh TG, Fang S, Cayabyab F, Zhu Q, Zhang T, Leblanc M, Liu S, He M, Waizenegger W, Gasser E, Schnabl B, Atkins AR, Yu RT, Knight R, Liddle C, Downes M, Evans RM. 2019. FXR regulates intestinal cancer stem cell proliferation. Cell 176:1098-1112. doi:10.1016/j.cell.2019.01.036 PMID:30794774 PMCID:PMC6701863
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