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    The role of M3 muscarinic receptor ligand-induced kinase signaling in colon cancer progression

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    Author
    Tolaymat, M.
    Larabee, S.M.
    Hu, S.
    Date
    2019
    Journal
    Cancers
    Publisher
    MDPI AG
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3390/cancers11030308
    Abstract
    Despite a reduction in incidence over the past decade, colon cancer remains the second most common cause of cancer death in the United States; recent demographics suggest this disease is now afflicting younger persons. M 3 muscarinic receptor (M 3 R) mRNA and protein are over-expressed in colon cancer, and M 3 R can be activated by both traditional (e.g., acetylcholine) and non-traditional (e.g., bile acids) muscarinic ligands. In this review, we weigh the data supporting a prominent role for key protein kinases downstream of M 3 R activation in promoting colon cancer progression and dissemination. Specifically, we explore the roles that downstream activation of the mitogen activated protein kinase/extracellular signal-related kinase (MAPK/ERK), protein kinase C, p38 MAPK, and phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathways play in mediating colon cancer cell proliferation, survival, migration and invasion. We assess the impact of M 3 R-stimulated induction of selected matrix metalloproteinases germane to these hallmarks of colon cancer progression. In this context, we also critically review the reproducibility of findings derived from a variety of in vivo and in vitro colon cancer models, and their fidelity to human disease. Finally, we summarize the therapeutic potential of targeting various steps from ligand-M 3 R interaction to the activation of key downstream molecules. Copyright 2019 by the authors. Licensee MDPI, Basel, Switzerland.
    Sponsors
    This research was funded by the United States (U.S.) Department of Veterans Affairs Biomedical Laboratory Research and Development Program, VA Merit Award grant numbers BX002129 and BX002777. Mazen Tolaymat and Shannon M. Larabee were supported by the U.S. National Institutes of Health, grant number T32 DK067872.
    Keyword
    Acetylcholine
    Bile acids
    Colon cancer
    Muscarinic ligands
    Muscarinic receptors
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85063375426&doi=10.3390%2fcancers11030308&partnerID=40&md5=d89d7c2cfd0dce193dfb51c93d5363cc; http://hdl.handle.net/10713/10796
    ae974a485f413a2113503eed53cd6c53
    10.3390/cancers11030308
    Scopus Count
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    UMB Open Access Articles 2019

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