Western Diet Deregulates Bile Acid Homeostasis, Cell Proliferation, and Tumorigenesis in Colon

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dc.contributor.author Dermadi, Denis
dc.contributor.author Valo, Satu
dc.contributor.author Ollila, Saara
dc.contributor.author Soliymani, Rabah
dc.contributor.author Sipari, Nina
dc.contributor.author Pussila, Marjaana
dc.contributor.author Sarantaus, Laura
dc.contributor.author Linden, Jere
dc.contributor.author Baumann, Marc
dc.contributor.author Nystrom, Minna
dc.date.accessioned 2018-07-06T21:21:53Z
dc.date.available 2021-12-17T22:02:51Z
dc.date.issued 2017-06-15
dc.identifier.citation Dermadi , D , Valo , S , Ollila , S , Soliymani , R , Sipari , N , Pussila , M , Sarantaus , L , Linden , J , Baumann , M & Nystrom , M 2017 , ' Western Diet Deregulates Bile Acid Homeostasis, Cell Proliferation, and Tumorigenesis in Colon ' , Cancer Research , vol. 77 , no. 12 , pp. 3352-3363 . https://doi.org/10.1158/0008-5472.CAN-16-2860
dc.identifier.other PURE: 86599481
dc.identifier.other PURE UUID: 0e0abc66-1244-4315-8b29-5c3594f7a523
dc.identifier.other WOS: 000403328500022
dc.identifier.other Scopus: 85021136321
dc.identifier.other ORCID: /0000-0002-5494-0685/work/44697653
dc.identifier.other ORCID: /0000-0003-0827-0243/work/39202633
dc.identifier.other ORCID: /0000-0001-9872-3626/work/52200387
dc.identifier.uri http://hdl.handle.net/10138/237004
dc.description.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 in-creased crypt depth and colon cell proliferation. Despite increased luminal BA, colonocytes from WD-fed mice exhibited decreased expression of the BA transporters FABP6, OST beta, 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. (C) 2017 AACR. en
dc.format.extent 12
dc.language.iso eng
dc.relation.ispartof Cancer Research
dc.rights unspecified
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject FARNESOID-X RECEPTOR
dc.subject NEGATIVE FEEDBACK-REGULATION
dc.subject NUCLEAR RECEPTOR
dc.subject BINDING PROTEIN
dc.subject DOWN-REGULATION
dc.subject HIGH-FAT
dc.subject TRANSPORTER
dc.subject CANCER
dc.subject MICE
dc.subject INTESTINE
dc.subject 3122 Cancers
dc.title Western Diet Deregulates Bile Acid Homeostasis, Cell Proliferation, and Tumorigenesis in Colon en
dc.type Article
dc.contributor.organization Biosciences
dc.contributor.organization Medicum
dc.contributor.organization Department of Medical and Clinical Genetics
dc.contributor.organization Research Programs Unit
dc.contributor.organization Department of Biochemistry and Developmental Biology
dc.contributor.organization Genetics
dc.contributor.organization Departments of Faculty of Veterinary Medicine
dc.contributor.organization Veterinary Pathology and Parasitology
dc.contributor.organization Veterinary Biosciences
dc.contributor.organization Marc Baumann / Principal Investigator
dc.contributor.organization Minna Nyström / Principal Investigator
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1158/0008-5472.CAN-16-2860
dc.relation.issn 0008-5472
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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