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    Monoacylglycerol lipase exerts dual control over endocannabinoid and fatty acid pathways to support prostate cancer

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    Author
    Ward, Anna
    Affiliation
    The University of Arizona College of Medicine - Phoenix
    Issue Date
    2013-03
    MeSH Subjects
    Prostatic Neoplasms
    Monoacylglycerol Lipases
    Mentor
    Nomura, Daniel
    
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    Rights
    Copyright © is held by the author. Digital access to this material is made possible by the College of Medicine - Phoenix, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
    Collection Information
    This item is part of the College of Medicine - Phoenix Scholarly Projects 2013 collection. For more information, contact the Phoenix Biomedical Campus Library at pbc-library@email.arizona.edu.
    Publisher
    The University of Arizona.
    Abstract
    Cancer cells couple heightened lipogenesis with lipolysis to produce fatty acid networks that support malignancy. Monoacylglycerol lipase (MAGL) plays a principal role in this process by converting monoglycerides, including the endocannabinoid 2-arachidonoylglycerol (2-AG), to free fatty acids. Here, we show that MAGL is elevated in androgen-independent versus androgen-dependent human prostate cancer cell lines, and that pharmacological or RNA-interference disruption of this enzyme impairs prostate cancer aggressiveness. These effects were partially reversed by treatment with fatty acids or a cannabinoid receptor-1 (CB1) antagonist, and fully reversed by co-treatment with both agents. We further show that MAGL is part of a gene signature correlated with epithelial-to-mesenchymal transition and the stem-like properties of cancer cells, supporting a role for this enzyme in pro-tumorigenic metabolism that, for prostate cancer, involves the dual control of endocannabinoid and fatty acid pathways.
    Description
    A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.
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    Scholarly Projects 2013

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