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    Targeted Metabolomics Identifies the Cytochrome P450 Monooxygenase Eicosanoid Pathway as a Novel Therapeutic Target of Colon Tumorigenesis

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    Authors
    Wang, Weicang
    Yang, Jun
    Edin, Matthew L.
    Wang, Yuxin
    Luo, Ying
    Wan, Debin
    Yang, Haixia
    Song, Chun-Qing
    Xue, Wen
    Sanidad, Katherine Z.
    Song, Mingyue
    Bisbee, Heather A.
    Bradbury, Jennifer A.
    Nan, Guanjun
    Zhang, Jianan
    Shih, Pei-An Betty
    Lee, Kin Sing Stephen
    Minter, Lisa M.
    Kim, Daeyoung
    Xiao, Hang
    Liu, Jun-Yan
    Hammock, Bruce D.
    Zeldin, Darryl C.
    Zhang, Guodong
    Show allShow less
    UMass Chan Affiliations
    Li Weibo Institute for Rare Diseases Research
    Department of Molecular, Cell and Cancer Biology
    Program in Molecular Medicine
    RNA Therapeutics Institute
    Document Type
    Journal Article
    Publication Date
    2019-04-15
    Keywords
    Biochemistry
    Cancer Biology
    Enzymes and Coenzymes
    Molecular Biology
    Neoplasms
    
    Metadata
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    Link to Full Text
    https://doi.org/10.1158/0008-5472.CAN-18-3221
    Abstract
    Colon cancer is the third most common cancer and the second leading cause of cancer-related death in the United States, emphasizing the need for the discovery of new cellular targets. Using a metabolomics approach, we report here that epoxygenated fatty acids (EpFA), which are eicosanoid metabolites produced by cytochrome P450 (CYP) monooxygenases, were increased in both the plasma and colon of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon cancer mice. CYP monooxygenases were overexpressed in colon tumor tissues and colon cancer cells. Pharmacologic inhibition or genetic ablation of CYP monooxygenases suppressed AOM/DSS-induced colon tumorigenesis in vivo. In addition, treatment with 12,13-epoxyoctadecenoic acid (EpOME), which is a metabolite of CYP monooxygenase produced from linoleic acid, increased cytokine production and JNK phosphorylation in vitro and exacerbated AOM/DSS-induced colon tumorigenesis in vivo. Together, these results demonstrate that the previously unappreciated CYP monooxygenase pathway is upregulated in colon cancer, contributes to its pathogenesis, and could be therapeutically explored for preventing or treating colon cancer. SIGNIFICANCE: This study finds that the previously unappreciated CYP monooxygenase eicosanoid pathway is deregulated in colon cancer and contributes to colon tumorigenesis.
    Source

    Cancer Res. 2019 Apr 15;79(8):1822-1830. doi: 10.1158/0008-5472.CAN-18-3221. Epub 2019 Feb 25. Link to article on publisher's site

    DOI
    10.1158/0008-5472.CAN-18-3221
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/44499
    PubMed ID
    30803995
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    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1158/0008-5472.CAN-18-3221
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